Rapid quantification and validation of lipid concentrations within liposomes

Quantification of the lipid content in liposomal adjuvants for subunit vaccine formulation is of extreme importance, since this concentration impacts both efficacy and stability. In this paper, we outline a high performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) method that allows for the rapid and simultaneous quantification of lipid concentrations within liposomal systems prepared by three liposomal manufacturing techniques (lipid film hydration, high shear mixing, and microfluidics). The ELSD system was used to quantify four lipids: 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), cholesterol, dimethyldioctadecylammonium (DDA) bromide, and D-(+)-trehalose 6,6′-dibehenate (TDB). The developed method offers rapidity, high sensitivity, direct linearity, and a good consistency on the responses (R2 > 0.993 for the four lipids tested). The corresponding limit of detection (LOD) and limit of quantification (LOQ) were 0.11 and 0.36 mg/mL (DMPC), 0.02 and 0.80 mg/mL (cholesterol), 0.06 and 0.20 mg/mL (DDA), and 0.05 and 0.16 mg/mL (TDB), respectively. HPLC-ELSD was shown to be a rapid and effective method for the quantification of lipids within liposome formulations without the need for lipid extraction processes.

Respuesta terapéutica a la infiltración epidural con metilprednisolona más bupivacaína vs. meloxicam + calor húmedo y ejercicios, en pacientes con lumbalgia crónica. Hospitales Vicente Corral Moscoso, Monte Sinaí y Maternidad San Martín de Porres. Cuenca, 2005

Es un estudio clínico controlado en el que se incluyeron 88 pacientes de ambos sexos en dos grupos asignados aleatoriamente. El grupo infiltración (n = 44) recibió 80 mg de metilprednisolona + 25 mg de bupivacaína al 0.5con epinefrina al 1:200.000 y el grupo conservador (n = 44) recibió 15 mg diarios por vía oral de meloxicam + calor local húmedo y ejercicios de fortalecimiento. En cada grupo hubo 22 pacientes con patología discal diagnosticada por tomografía axial computadorizada. Se evaluó el dolor según la Escala Análoga Visual y la discapacidad según la Escala de Roland Morris, en seis controles, cada semana por 4 semanas y a los 3 y 6 meses. Resultados. En condiciones basales los grupos fueron comparables en la valoración del dolor y la discapacidad. En los dos grupos de estudio no se encontraron diferencias significativas, en cuanto se refiere a la discapacidad y el dolor , sin embargo en el seguimiento tanto la infiltración como el tratamiento conservador produjo alivio inmediato de la sintomatología pero en los controles posteriores el tratamiento conservador tuvo una mejor respuesta en los dos parámetros, dolor a los 3 meses (p = 0.027) y 6 meses (p = 0.039) , discapacidad a la cuarta semana (p = 0.019), El análisis por subgrupos según patología discal no tuvo diferencias significativas. En la escala de Likert que valora la mejoría desde la percepción del paciente hubo una tendencia a beneficiar al grupo que recibió el tratamiento conservador RR 0.8 (IC95: 0.55-1.16). Conclusiones. La infiltración epidural de 80 mg de metilprednisolona + 15 mg de bupivacaína para tratamiento de la lumbalgia crónica con o sin patología discal tuvo igual respuesta que 15 mg diarios de meloxicam por vía oral más terapia física, en un seguimiento de 6 meses

Anestesia espinal con lidocaína isobárica e hiperbárica para cesárea: Hospital Vicente Corral Moscoso, Cuenca 2005-2006

Este es un ensayo clínico controlado realizado en 327 pacientes ASA II, sometidas a cesárea, distribuidas aleatoriamente en dos grupos iguales para identificar las variaciones hemodinámicas y nivel metamérico, al aplicar Anestesia Intratecal con Lidocaína Isobárica al 2(AILI) comparada con Lidocaína Hiperbárica al 5(AILH), ambas a dosis de 80 mg. Resultados: la AILI, se mantuvo en determinadas metámeras sin sustancial variabilidad, comportamiento totalmente contrario a la AILH. Las diferencias estadísticas en la presión sistólica, diastólica, y frecuencia cardiaca, entre ambos tipos de anestesia no fueron significativas. La hipotensión se presentó en 32,9con AILI, y 54con AILH; siendo tratada con 2,26 mg (ñ 3.65) y 3,93 mg (ñ 4,26) de efedrina respectivamente. (p> 0.05). Con AILI se presentaron 4 casos de bloqueo raquídeo alto más dificultad respiratoria y, con AILH 3 casos, de los cuales solo 2 presentaron dificultad respiratoria. Conclusión: la AILI produce un bloqueo nervioso más predecible que la AILH. Los valores hemodinámicos y la incidencia de complicaciones, entre ambos anestésicos fueron semejantes

Medición de la profundidad anestésica y memoria durante anestesia general mediante el cerebral state monitor (csm x06)

Este es un ensayo clínico controlado realizado en 327 pacientes ASA II, sometidas a cesárea, distribuidas aleatoriamente en dos grupos iguales para identificar las variaciones hemodinámicas y nivel metamérico, al aplicar Anestesia Intratecal con Lidocaína Isobárica al 2(AILI) comparada con Lidocaína Hiperbárica al 5(AILH), ambas a dosis de 80 mg. Resultados: la AILI, se mantuvo en determinadas metámeras sin sustancial variabilidad, comportamiento totalmente contrario a la AILH. Las diferencias estadísticas en la presión sistólica, diastólica, y frecuencia cardiaca, entre ambos tipos de anestesia no fueron significativas. La hipotensión se presentó en 32,9con AILI, y 54con AILH; siendo tratada con 2,26 mg (ñ 3.65) y 3,93 mg (ñ 4,26) de efedrina respectivamente. (p> 0.05). Con AILI se presentaron 4 casos de bloqueo raquídeo alto más dificultad respiratoria y, con AILH 3 casos, de los cuales solo 2 presentaron dificultad respiratoria. Conclusión: la AILI produce un bloqueo nervioso más predecible que la AILH. Los valores hemodinámicos y la incidencia de complicaciones, entre ambos anestésicos fueron semejantes

Severe Statin-induced Rhabdomyolysis following Cholestatic Hepatitis induced by Amoxicillin-clavulanate

We report the case of an 86-year-old man with a past history of coronary disease admitted to our internal medicine department for severe asthenia and weakness due to rhabdomyolysis. Three days earlier, he had been discharged from a gastroenterology unit with a diagnosis of amoxicillin–clavulanate-induced acute cholestatic hepatitis. A review of his drugs revealed that he had taken atorvastatin 10 mg daily in the previous six years, without clinical or laboratory signs of myopathy. Atorvastatin was therefore stopped, with gradual improvement of the rhabdomyolysis. All concomitant drug therapy needs to be reassessed in elderly patients, especially when they become acutely ill.

Produção de carboidratos a partir do efluente de laticínios tratado por cianobactéria

Nesta tese foi demonstrado o potencial de produção de carboidratos por Aphanothece microscopica Nägeli cultivada no efluente oriundo de uma indústria de laticínios. Para tanto, o trabalho é composto de quatro artigos que objetivaram avaliar a produção de carboidratos em função da temperatura, inóculo e razões C/N e N/P do elfluente, bem como a possibilidade de reúso da água residuária. Foram utilizadas temperaturas de (10, 20 e 30ºC) e inóculo (100, 200 e 300 mg.L-1). A melhor condição indicada foi quando utilizou-se a temperatura de 30°C e 200 mg.L-1 de inóculo. Na sequência, considerando a temperatura e a concentração celular selecionada, foi estudada a influência das razões C/N e N/P na produção de carboidratos. Para tal, C/N (20, 40 e 60) e N/P (5, 10 e 15) na produção de carboidratos extracelulares foram avaliadas em cultivos a 30°C, tendo como inóculo 200 mg.L-1. Os melhores resultados obtidos, foram quando foi utilizado C/N 60 e N/P 10. Uma vez definidas as melhores condições de produção de carboidratos, foi estudado o processo de separação de biomassa do meio de cultivo, a partir dos coagulantes FeCl3, Al2(SO4)3 e tanino. O efeito dos coagulantes na separação da biomassa foram estudados, quanto ao pH (6,0, 7,0 e 8,0) e concentração de coagulantes (50, 300 e 550 mg.L-1), utilizando como parâmetro de medida, a eficiência de remoção de DQO, turbidez e sólidos suspensos (SS). Os resultados demonstraram que as concentrações de coagulantes influenciaram significativamente ao nível de significância de 5 %, na separação da biomassa, com eficiência significativa na remoção da DQO, turbidez e SS. A melhor condição avaliada foi a que utilizou tanino na concentração de 300 mg.L-1 e pH 7,0, o que resultou em uma água residuária com remoção média de 96 % da turbidez, com potencial de ser reutilizada. Por fim, foi realizada a identificação de carboidratos gerados por Aphanothece microscopica Nägeli. Os resultados evidenciaram uma biomassa com até 33,5 % de carboidratos totais, perfazendo uma fração de carboidratos extracelulares, na fase estacionária de crescimento celular, de aproximadamente 25 % e 8 % os carboidratos da parede celular. Ficou demonstrado ainda que a composição dos carboidratos extracelulares do microorganismo em estudo é constituído por mono e dissacarídeos perfazendo concentrações na ordem de 12,88 % de glicose, 3,54 % de rafinose, 3,43 % sacarose, 2,13 % de frutose e 2,45 % de ribose. Ficou demonstrado o potencial de produção de carboidratos por Aphanothece microscopica Nägeli quando cultivada no efluente da indústria de laticínios.

MULTIPLICAÇÃO E ALONGAMENTO IN VITRO DE CLONES HÍBRIDOS DE Eucalyptus globulus

Os híbridos de Eucalyptus globulus representam uma excelente alternativa para o setor de celulose e papel, em razão dos ganhos em qualidade da madeira para a fabricação de celulose. Entretanto, estes híbridos têm apresentado recalcitrância ao enraizamento adventício. Assim, a micropropagação é apontada como a técnica para o rejuvenescimento desses híbridos adultos, viabilizando a propagação clonal dos mesmos. O presente trabalho avaliou o cultivo in vitro de três clones de Eucalyptus grandis x Eucalyptus globulus e de três clones de Eucalyptus urophylla x Eucalyptus globulus, em relação à multiplicação in vitro, no meio MS suplementado com 0,5 mg L-1 de BAP e 0,01 mg L-1 de ANA, bem como o efeito das concentrações de 0,25; 0,50; 0,75 e 1,0 mg L-1 de AIB e dos meios de cultura MS e JADS no alongamento in vitro das brotações. Os clones diferiram quanto à multiplicação in vitro das brotações e apresentaram uma taxa de multiplicação média dos clones de 3,0 tufos de brotações em cada subcultivo, ao longo dos 25 subcultivos realizados. No alongamento in vitro, os clones diferiram quanto às concentrações de AIB adequadas para provocar o alongamento, bem como em relação aos meios de cultura MS e JADS. O intervalo médio entre 0,40 e 0,80 mg L-1 de AIB proporcionou o maior número e comprimento das brotações alongadas in vitro e com maior vigor.

Magnetic carbon xerogels for the catalytic wet peroxide oxidation of sulfamethoxazole in environmentally relevant water matrices

Novel magnetic carbon xerogels consisting of interconnected carbon microspheres with iron and/or cobalt microparticles embedded in their structure were developed by a simple route. As inferred from the characterization data, materials with distinctive properties may be directly obtained upon inclusion of iron and/or cobalt precursors during the sol-gel polymerization of resorcinol and formaldehyde, followed by thermal annealing. The unique properties of these magnetic carbon xerogels were explored in the catalytic wet peroxide oxidation (CWPO) of an antimicrobial agent typically found throughout the urban water cycle – sulfamethoxazole (SMX). A clear synergistic effect arises from the inclusion of cobalt and iron in carbon xerogels (CX/CoFe),the resulting magnetic material revealing a better performance in the CWPO of SMX at the ppb level(500 microg L−1) when compared to that of monometallic carbon xerogels containing only iron or cobalt.This effect was ascribed to the increased accessibility of highly active iron species promoted by the simultaneous incorporation of cobalt.The performance of the CWPO process in the presence of CX/CoFe was also evaluated in environmentally relevant water matrices, namely in drinking water and secondary treated wastewater, considered in addition to ultrapure water. It was found that the performance decreases when applied to more complex water and wastewater samples. Nevertheless, the ability of the CWPO technology for the elimination of SMX in secondary treated wastewater was unequivocally shown, with 96.8% of its initial content being removed after 6 h of reaction in the presence of CX/CoFe, at atmospheric pressure, room temperature(T = 25◦C), pH = 3, [H2O2]0= 500 mg L−1and catalyst load = 80 mg L−1. A similar performance (97.8% SMX removal) is obtained in 30 min when the reaction temperature is slightly increased up to 60◦C in an ultra-pure water matrix. Synthetic water containing humic acid, bicarbonate, sulphate or chloride, was also tested. The results suggest the scavenging effect of the different anions considered, as well as the negative impact of dissolved organic matter typically found in secondary treated wastewater, as simulated by the presence of humic acid.An in-situ magnetic separation procedure was applied for catalyst recovery and re-use during reusability cycles performed to mimic real-scale applications. CWPO runs performed with increased SMX concentration (10 mg L−1), under a water treatment process intensification approach, allowed to evalu-ate the mineralization levels obtained, the antimicrobial activity of the treated water, and to propose adegradation mechanism for the CWPO of SMX.

Telmisartan to prevent recurrent stroke and cardiovascular events

Background Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin–angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin–angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke. Methods In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes. Results The median interval from stroke to randomization was 15 days. During a mean followup of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P = 0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P = 0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P = 0.10). Conclusions Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062.)

Equilibrium Sorption Studies of Hg (II) Ions from Aqueous Solution using Powdered Swamp Arum ( Lasimorpha senegalensis ) Seeds.

The potential of swamp arum ( Lasimorpha senegalensis ) seeds as a low-cost adsorbent for the removal of Hg (II) ions from aqueous solution was investigated in this study. The influence of initial metal concentration on the percent adsorption of Hg (II) ions onto powdered swamp arum seeds was studied in a batch system and the filtrate was analyzed using Atomic Absorption Spectrometry (AAS). The percent adsorbed for 10, 20, 40, 60 and 80 mg/L of the aqueous solution were 97.7, 98.9, 99.3, 99.7, and 96.5% respectively. Three isotherms; Langmuir, Freundlich, and BET were used to model the equilibrium sorption of Hg (II) ions onto powdered swamp arum seeds, with a correlation coefficient of 0.998, 0.784 and0.842 respectively. The Langmuir model fitted the equilibrium data best, with a correlation coefficient of 0.998 and a maximum adsorption capacity qm, of 5.917 mg/g. Thus, indicating monolayer coverage on the adsorbent. The results showed that swamp arum seed have the potential to be applied as alternative lowcost biosorbent in the remediation of heavy metal contamination in waste water.

Effect of telmisartan on functional outcome, recurrence, and blood pressure in patients with acute mild ischemic stroke: a PRoFESS subgroup analysis

Background and Purpose—High blood pressure (BP) is common in acute ischemic stroke and associated independently with a poor functional outcome. However, the management of BP acutely remains unclear because no large trials have been completed. Methods—The factorial PRoFESS secondary stroke prevention trial assessed BP-lowering and antiplatelet strategies in 20 332 patients; 1360 were enrolled within 72 hours of ischemic stroke, with telmisartan (angiotensin receptor antagonist, 80 mg/d, n647) vs placebo (n713). For this nonprespecified subgroup analysis, the primary outcome was functional outcome at 30 days; secondary outcomes included death, recurrence, and hemodynamic measures at up to 90 days. Analyses were adjusted for baseline prognostic variables and antiplatelet assignment. Results—Patients were representative of the whole trial (age 67 years, male 65%, baseline BP 147/84 mm Hg, small artery disease 60%, NIHSS 3) and baseline variables were similar between treatment groups. The mean time from stroke to recruitment was 58 hours. Combined death or dependency (modified Rankin scale: OR, 1.03; 95% CI, 0.84–1.26; P0.81; death: OR, 1.05; 95% CI, 0.27–4.04; and stroke recurrence: OR, 1.40; 95% CI, 0.68–2.89; P0.36) did not differ between the treatment groups. In comparison with placebo, telmisartan lowered BP (141/82 vs 135/78 mmHg, difference 6 to 7 mmHg and 2 to 4 mmHg; P0.001), pulse pressure (3 to 4 mmHg; P0.002), and rate-pressure product (466 mmHg.bpm; P0.0004). Conclusion—Treatment with telmisartan in 1360 patients with acute mild ischemic stroke and mildly elevated BP appeared to be safe with no excess in adverse events, was not associated with a significant effect on functional dependency, death, or recurrence, and modestly lowered BP.

Compostos bioativos de microalgas com interesse no tratamento da diabetes

Dissertação de Mestrado, Biologia Molecular e Microbiana, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2016

Clinical efficacy of paclitaxel in the treatment of mid-stage and advanced malignant gastric cancer, and effect of nursing interventions

Purpose: To investigate the clinical efficacy of paclitaxel combined with additional chemotherapy for mid-stage and advanced malignant tumors, and the benefits afforded by scientific nursing. Methods: Patients with mid-stage and advanced gastric cancer were randomly divided into test and control groups. Control group was given intravenous chemotherapy (400 mg/m2 fluorouracil and 2500 mg/m2 cisplatin) and nursed conventionally, while the test group was additionally treated with 80 mg/m2 paclitaxel and underwent special scientific nursing. Clinical effects and changes in the rates of apoptosis and cell proliferation were recorded. The effect of applying scientific nursing on therapeutic outcomes was also evaluated. Results: The overall rate of treatment effectiveness, clinical control rate, mean apoptosis and proliferation rates in the test group were 56.40, 92.30, (7.10 ± 3.17 and 28.70 ± 3.22 %, respectively, while, in the control group, the values were 38.50, 64.10, 25.40 ± 2.67 and 32.60 ± 2.93 %, respectively. The differences were all statistically significant (p < 0.05). In terms of nursing efficacy, the test group had a lower pain score and higher quality-of-life scores (Karnofsky performance status score) than control group. There was no significant difference in the incidence of adverse reactions between the two groups (p > 0.05). Conclusion: Paclitaxel has a significant effect when used to treat mid-stage and advanced gastric cancer. Moreover, additional nursing not only enhances the therapeutic effect but also improves prognosis and quality-of-life.

Medición de la profundidad anestésica y memoria durante anestesia general mediante el cerebral state monitor (csm x06)

Este es un ensayo clínico controlado realizado en 327 pacientes ASA II, sometidas a cesárea, distribuidas aleatoriamente en dos grupos iguales para identificar las variaciones hemodinámicas y nivel metamérico, al aplicar Anestesia Intratecal con Lidocaína Isobárica al 2(AILI) comparada con Lidocaína Hiperbárica al 5(AILH), ambas a dosis de 80 mg. Resultados: la AILI, se mantuvo en determinadas metámeras sin sustancial variabilidad, comportamiento totalmente contrario a la AILH. Las diferencias estadísticas en la presión sistólica, diastólica, y frecuencia cardiaca, entre ambos tipos de anestesia no fueron significativas. La hipotensión se presentó en 32,9con AILI, y 54con AILH; siendo tratada con 2,26 mg (ñ 3.65) y 3,93 mg (ñ 4,26) de efedrina respectivamente. (p> 0.05). Con AILI se presentaron 4 casos de bloqueo raquídeo alto más dificultad respiratoria y, con AILH 3 casos, de los cuales solo 2 presentaron dificultad respiratoria. Conclusión: la AILI produce un bloqueo nervioso más predecible que la AILH. Los valores hemodinámicos y la incidencia de complicaciones, entre ambos anestésicos fueron semejantes

Utilización de antimicrobianos en las infecciones odontogénicas en niños y adolescentes: análisis farmacocinético/farmacodinámico (PK/PD)

El objetivo de este estudio es evaluar la eficacia de los tratamientos más utilizados en infecciones odontogénicas en niños y adolescentes aplicando criterios farmacocinéticos/farmacodinámicos (PK/PD). Se han simulado las curvas de concentración plasmática libre-tiempo a partir de parámetros farmacocinéticos medios de amoxicilina, amoxicilina-ácido clavulánico, cefuroxima axetilo, espiramicina, clindamicina, azitromicina y metronidazol. Para los antibióticos con actividad dependiente del tiempo, se ha calculado el tiempo durante el cual las concentraciones permanecen por encima de la concentración inhibitoria mínima (CIM90) de los microorganismos (T>CIM). Para los antimicrobianos con actividad dependiente de la concentración, se ha calculado el cociente entre el área bajo la curva y la CIM90 (ABC/CIM90). Con amoxicilina-ácido clavulánico (80 mg/kg/día) se han obtenido índices de eficacia adecuados frente a los microorganismos estudiados (T > CIM > 40%), excepto paraVeillonella spp. Clindamicina (40 mg/kg/día) también ha presentado índices PK/PD adecuados frente a la mayoría de los patógenos, excepto Lactobacillus, Actinobacillus actinomycetemcomitans, Peptostreptococcus resistente a penicilina y Eikenella corrodens. Con dosis altas de amoxicilina los resultados no han sido satisfactorios frente a varias especies bacterianas. Con azitromicina y metronidazol no se han alcanzado valores adecuados frente a la mayoría de patógenos (ABC/CIM90 < 25). En conclusión, el tratamiento empírico más adecuado en infecciones odontogénicas en niños y adolescentes es amoxicilina-ácido clavulánico en altas dosis de amoxicilina, aunque se puede utilizar como alternativa clindamicina. Sería conveniente confirmar estos resultados mediante ensayos clínicos, para cuyo diseño y evaluación podría ser de gran utilidad la aplicación de estudios PK/PD.