Possible in vivo mechanisms involved in photodynamic therapy using tetrapyrrolic macrocycles

Photodynamic therapy (PDT) mediated by oxidative stress causes direct tumor cell damage as well as microvascular injury. To improve this treatment new photosensitizers are being synthesized and tested. We evaluated the effects of PDT with 5,10,15,20-tetrakis(4-methoxyphenyl)-porphyrin (TMPP) and its zinc complex (ZnTMPP) on tumor levels of malondialdehyde (MDA), reduced glutathione (GSH) and cytokines, and on the activity of caspase-3 and metalloproteases (MMP-2 and -9) and attempted to correlate them with the histological alterations of tumors in 3-month-old male Wistar rats, 180 ± 20 g, bearing Walker 256 carcinosarcoma. Rats were randomly divided into five groups: group 1, ZnTMPP+irradiation (IR) 10 mg/kg body weight; group 2, TMPP+IR 10 mg/kg body weight; group 3, 5-aminolevulinic acid (5-ALA+IR) 250 mg/kg body weight; group 4, control, no treatment; group 5, only IR. The tumors were irradiated for 15 min with red light (100 J/cm², 10 kHz, 685 nm) 24 h after drug administration. Tumor tissue levels of MDA (1.1 ± 0.7 in ZnTMPP vs 0.1 ± 0.04 nmol/mg protein in control) and TNF-α (43.5 ± 31.2 in ZnTMPP vs 17.3 ± 1.2 pg/mg protein in control) were significantly higher in treated tumors than in controls. Higher caspase-3 activity (1.9 ± 0.9 in TMPP vs 1.1 ± 0.6 OD/mg protein in control) as well as the activation of MMP-2 (P < 0.05) were also observed in tumors. These parameters were correlated (Spearman correlation, P < 0.05) with the histological alterations. These results suggest that PDT activates the innate immune system and that the effects of PDT with TMPP and ZnTMPP are mediated by reactive oxygen species, which induce cell membrane damage and apoptosis.

Early responses of the STAT3 pathway to platinum drugs are associated with cisplatin resistance in epithelial ovarian cancer

Cisplatin resistance remains one of the major obstacles when treating epithelial ovarian cancer. Because oxaliplatin and nedaplatin are effective against cisplatin-resistant ovarian cancer in clinical trials and signal transducer and activator of transcription 3 (STAT3) is associated with cisplatin resistance, we investigated whether overcoming cisplatin resistance by oxaliplatin and nedaplatin was associated with the STAT3 pathway in ovarian cancer. Alamar blue, clonogenic, and wound healing assays, and Western blot analysis were used to compare the effects of platinum drugs in SKOV-3 cells. At an equitoxic dose, oxaliplatin and nedaplatin exhibited similar inhibitory effects on colony-forming ability and greater inhibition on cell motility than cisplatin in ovarian cancer. Early in the time course of drug administration, cisplatin increased the expression of pSTAT3 (Tyr705), STAT3α, VEGF, survivin, and Bcl-XL, while oxaliplatin and nedaplatin exhibited the opposite effects, and upregulated pSTAT3 (Ser727) and STAT3β. The STAT3 pathway responded early to platinum drugs associated with cisplatin resistance in epithelial ovarian cancer and provided a rationale for new therapeutic strategies to reverse cisplatin resistance.

Microextração em fase sólida de 6-pentil-α-pirona produzida por fermentação em estado sólido

A substância 6-pentil-α-pirona (6-PP) é uma lactona com aroma característico de coco e uso aprovado pela agência americana Food and Drug Administration (FDA). O presente trabalho teve como objetivo ajustar as condições de microextração em fase sólida em headspace para a quantificação por cromatografia gasosa de 6-PP produzida pelo fungo Trichoderma harzianum a partir do pó da casca de coco verde. Para isto, foi realizado um estudo em que soluções padronizadas de 6-PP foram adicionadas ao pó da casca de coco verde. A substância foi extraída por uma fibra de polidimetilsiloxano. Agitação e adição de solução de NaCl a 25% (p/v) resultaram em melhor reprodutibilidade nas análises. Um planejamento composto central foi empregado para estudar três fatores: temperatura de extração, tempo de condicionamento e tempo de extração. Boas respostas foram obtidas com a temperatura de 79 °C e tempo de extração de 29 minutos. O efeito da variável tempo de condicionamento não foi significativo e foi fixado em 2 minutos. Após o desenvolvimento do método analítico, este foi empregado para determinar a produção de 6-PP por fermentação em estado sólido realizada por Trichoderma harzianum e com o uso de pó da casca de coco verde como suporte para o processo.

The effect of a diet education with six iso-caloric meals on the body weight and blood glucose of diabetes type 2 patients

The treatment of Diabetes should not only be sought through drug administration; diet is also a part of its treatment. The aim of this study was to determine the effect of a diet with six meals having equal calories on the body weight and blood glucose on diabetes type 2 patients. This research is an Experimental study conducted in 2009 on 181 patients with diabetes. The patients visited the IDSF (Iranian Diabetes Society of Fars) weekly and the patients to be studied were randomly divided into two groups of 85 and 96 patients, respectively. The participants were repeatedly requested to consume their calculated calorie in six equal parts. The average age in the Experimental and Control groups were 51.2 ± 13.3 and 53.1 ± 9.4, respectively. The mean body weight and fasting blood glucose at the beginning of the study in Experimental and Control groups were 66.3 ± 9.4 and 69.1 ± 11.1 kg, 198.9 ± 35.1, and 199.8 ± 39.1 mg.dL-1, respectively. At the end of the study, however, the values were 63.5 ± 7.5 and 66.98 ± 9 kg, 139.5 ± 34.6 and 164.2 ± 22.1 mg.dL-1, respectively. Only the mean fasting blood glucose at the end of the study revealed a significant difference (p-value = 0.001). The results show that educating those afflicted with Diabetes Type 2 aiming at changing their diet can greatly help them manage their blood glucose.

Investigation of the role of the nucleus accumbens in amphetamine-induced 50 kHz ultrasonic vocalizations in the rat

There is extensive evidence that the mesolimbic dopamine system underlies the production of 50 kHz ultrasonic vocalizations in rats. In particular, the shell of the nucleus accumbens is associated with generation of frequency modulated 50 kHz calls (a specific type of 50 kHz call which can be subdivided into various subtypes). There is also evidence that amphetamine administered systemically preferentially increases the proportion of trill and step calls compared to other frequency modulated 50 kHz subtypes. The purpose of this study was to investigate the effect of drug administration route and the role of the nucleus accumbens shell in amphetamine-induced 50 kHz call profile in the rat. Three experiments investigated this by using subcutaneous and intra-accumbens microinjections of amphetamine, as well as procaine (a local anesthetic) blockade of the nucleus accumbens. Ultrasonic vocalizations were recorded digitally from 24 rats and were analysed for sonographic structure based on general call parameters. The results of the three experiments were partially supportive of the hypotheses. Systemic amphetamine was found to induce greater bandwidth in 50 kHz calling compared to spontaneous calls in a vehicle condition. Systemic amphetamine was also found to preferentially increase the proportion of trill and step subtypes compared to vehicle. Moreover, there was no difference in the proportions of 50 kHz subtypes resulting from intracerebral or systemic application of amphetamine. There was, however, a significant difference for bandwidth, with systemic amphetamine inducing greater bandwidth over intraaccumbens application. Procaine blockade of the nucleus accumbens shell paired with subcutaneous amphetamine produced no difference in bandwidth of calls compared with those after a vehicle pre-treatment similarly paired. There was no reduction in the proportions of trill and step 50 kHz subtypes as well, with the procaine condition showing significantly greater proportion of step calls. The results of the study support a role for the iii nucleus accumbens shell in the amphetamine-induced changes on 50 kHz call profile. They also indicate there are more regions and pathways involved in generating 50 kHz calls than the projections from the ventral tegmental area to the nucleus accumbens. The implications of this work are that frequency modulated 50 kHz subtypes may be generated by distinct neurophysiological mechanisms and may represent a profitable avenue for investigating different circuits of 50 kHz call categories in the rat.

Potential Urinary Protein Biomarker Candidates for the Accurate Detection of Prostate Cancer among Benign Prostatic Hyperplasia Patients

Globally, Prostate cancer (PCa) is the most frequently occurring non-cutaneous cancer, and is the second highest cause of cancer mortality in men. Serum prostate specific antigen (PSA) has been the standard in PCa screening since its approval by the American Food & Drug Administration (FDA) in 1994. Currently, PSA is used as an indicator for PCa - patients with a serum PSA level above 4ng/mL will often undergo prostate biopsy to confirm cancer. Unfortunately fewer than similar to 30% of these men will biopsy positive for cancer, meaning that the majority of men undergo invasive biopsy with little benefit. Despite PSA's notoriously poor specificity (33%), there is still a significant lack of credible alternatives. Therefore an ideal biomarker that can specifically detect PCa at an early stage is urgently required. The aim of this study was to investigate the potential of using deregulation of urinary proteins in order to detect Prostate Cancer (PCa) among Benign Prostatic Hyperplasia (BPH). To identify the protein signatures specific for PCa, protein expression profiling of 8 PCa patients, 12 BPH patients and 10 healthy males was carried out using LC-MS/MS. This was followed by validating relative expression levels of proteins present in urine among all the patients using quantitative real time-PCR. This was followed by validating relative expression levels of proteins present in urine among all the patients using quantitative real time-PCR. This approach revealed that significant the down-regulation of Fibronectin and TP53INP2 was a characteristic event among PCa patients. Fibronectin mRNA down-regulation, was identified as offering improved specificity (50%) over PSA, albeit with a slightly lower although still acceptable sensitivity (75%) for detecting PCa. As for TP53INP2 on the other hand, its down-regulation was moderately sensitive (75%), identifying many patients with PCa, but was entirely non-specific (7%), designating many of the benign samples as malignant and being unable to accurately identify more than one negative.

Caractérisation de la réponse immunitaire cellulaire dirigée contre ARFP et cartographie des épitopes du génotype 3a lors de l’infection au virus de l’hépatite C

L’interféron-α pegylé en combinaison avec la ribavirin est le seul traitement approuvé pour le traitement de l’infection au virus de l’hépatite C (VHC). L’efficacité est de 50-75%, la thérapie est coûteuse et induit beaucoup d’effets secondaires. Il est impératif d’avoir une meilleure compréhension de la pathogenèse du VHC afin de développer des traitements plus efficaces ou un vaccin. À cette fin, notre approche est de caractériser la réponse immunitaire cellulaire induite par ARFP, un antigène nouveau et conservé chez le VHC, et de cartographier les épitopes de la réponse immunitaire cellulaire d’un patient infecté au génotype 3a ayant résolu spontanément. Le génotype 3a, étant prévalant chez les utilisateurs de drogues intraveineuses (IDUs) constitue 60% des nouvelles infections. Peu d’épitopes furent identifiés auparavant pour ce génotype, ce qui rend l’étude de la réponse immunitaire difficile chez cette population. Dans cette étude, pour la réponse immunitaire cellulaire dirigée contre ARFP, nous n’avons pas observé de différence significative entre les patients ayant résolu spontanément comparativement avec ceux ayant développé une infection persistante. Ceci suggère fortement que ARFP ne joue pas un rôle majeur lors de la résolution de l’infection aigue au VHC. Pour la caractérisation de la réponse immunitaire cellulaire chez un des patients infectés au génotype 3a, nous avons identifié et caractérisé 5 épitopes spécifiquement reconnus par des lymphocytes T, CD3+, CD4+ et CD8- : E2504-521, NS31064-1081, NS4b1759-1776, NS5a2074-2091, NS5b2421-2436. Nous avons comparé avec ceux connus pour le génotype 1a. Nous avons identifié 4 nouveaux épitopes. Enfin, l’épitope NS4b1759-1776, identifié auparavant, pourrait s’avérer être un candidat intéressant dans la mise au point d’un vaccin à base de peptides immunogéniques contre le VHC.

Rôle des kinines dans la physiopathologie des effets secondaires causés par les héparines contaminées d’origine chinoise : approche expérimentale

En janvier 2008, une éclosion de réactions anaphylactoïdes (RA) potentiellement mortelles associées à l’injection intraveineuse d’héparine manufacturées en Chine et contaminée par le chondroïtine sulfate hypersulfaté (CSHS) a forcé le rappel de ces dernières par la U.S. Food and Drug Administration. Ces RA ont rapidement été attribuées à la libération de la bradykinine (BK) suite à l’activation du système de contact par le CSHS. Cependant, aucune évidence expérimentale définitive n’est à ce jour venue appuyer directement cette hypothèse. En se basant sur le nombre de morts déclaré et associé à la contamination (>150 morts au niveau mondial) ainsi qu’aux données épidémiologiques, qui stipulent que 25% des patients ayant développés une RA aux États-Unis étaient essentiellement des insuffisant rénaux en dialyse traités au moyen d’un inhibiteur de l’enzyme de conversion de l’angiotensine (iECA), nous avons émis l’hypothèse suivante : les RA causées par l’injection intraveineuse d’héparine contaminée au CSHS sont de nature multifactorielle et complexe. Le but de notre travail est donc, dans un premier temps, d’évaluer le pouvoir kininoformateur du CSHS en présence d’un iECA et de le comparer à celui du sulfate de dextran, un activateur de référence du système de contact. Comme les RA associées à l’injection intraveineuse d’héparine contaminée par le CSHS se produisent généralement dans les premières minutes des séances de dialyse, nous allons étudier l’effet de la dilution du plasma sur la quantité de BK libérée en présence ou en absence d’un iECA. Nous allons également mesurer les profils cinétiques de la libération de la BK sur un plasma stimulé par différents lots d’héparine contaminée, et associée à des RA, et nous comparerons cette cinétique avec celles d’une héparine de référence complémentée ou non avec différentes concentrations de CSHS synthétique. Enfin, nous allons caractériser le profil de libération de la BK et de son métabolite actif, la des-Arg9-BK, dans le plasma de patients dialysé ayant présenté une RA associée à une membrane de dialyse chargée négativement. L’application de méthodes expérimentales développées dans notre laboratoire nous a permis de montrer, pour la première fois, que l’héparine contaminée au CSHS a la capacité de libérer la BK à des concentrations susceptibles d’expliquer le rôle de ce peptide inflammatoire dans la physiopathologie des RA causées par l’injection intraveineuse d’héparine d’origine chinoise contaminée au CSHS.

Prevalence of intestinal parasites in small ruminants and their senstivity to treatments with ethnobotanical remedies in Cholistan, Pakistan

Livestock production contributes substantially to the livelihoods of poor rural farmers in Pakistan; strengthening pastoral communities plays an imperative role in the country’s thrive for poverty alleviation. Intestinal helminths constitute a major threat for pastoral livestock keepers in the whole country because chronic infestation leads to distinct losses in livestock productivity, particularly the growth of young animals. Synthetic anthelmintics have long been considered the only effective way of controlling this problem but high prices, side effects and chemical residues/toxicity problems, or development of resistance, lead to their very limited use in many pastoral systems. Additionally, poor pastoralists in remote areas of Pakistan hardly have access to appropriate anthelmintic drugs, which are also relatively expensive due to the long routes of transportation. The search for new and more sustainable ways of supporting livestock keepers in remote areas has given rise to studies of ethno-botanicals or traditional plant-based remedies to be used in livestock health care. Plant-based remedies are cheap or free of cost, environmentally safe and generally create no problem of drug resistance; they thus might substitute allopathic drugs. Furthermore, these remedies are easily available in remote areas and simple to prepare and/or administer. Cholistan desert is a quite poor region of Pakistan and the majority of its inhabitants are practicing a nomadic life. The region’s total livestock population (1.29 million heads) is almost twice that of the human population. Livestock husbandry is the primordial occupation of the communities and traditionally wealth assessment was based on the number of animals, especially goats and sheep, owned by an individual. Fortunately, about 60% of this desert region is richly endowed with highly adapted grasses, shrubs and trees. This natural flora has a rich heritage of scientifically unexplored botanical pharmacopoeia. Against this background, the present research project that was conducted under the umbrella of the International Center for Development and Decent Work at Kassel University, focused on a development aspect: in the Cholistan desert region it was firstly examined how pastoralists manage their livestock, which major health problems they face for the different animal species, and which of the naturally occurring plants they use for the treatment of animal diseases (Chapter 2). For this purpose, a baseline survey was carried out across five locations in Cholistan, using a structured questionnaire to collect data from 100 livestock farmers (LF) and 20 local healers (LH). Most of LF and LH were illiterate (66%; 70%). On average, LH had larger herds (109 animals) than LF (85 animals) and were more experienced in livestock husbandry and management. On average LF spent about 163 Euro per year on the treatment of their livestock, with a huge variability in expenditures. Eighty-six traditional remedies based on 64 plants belonging to 43 families were used. Capparaceae was the botanical family with the largest number of species used (4), followed by Chenopodiaceae, Poaceae, Solanaceae and Zygophyllaceae (3). The plants Capparis decidua (n=55 mentions), Salsola foetida (n=52), Suaeda fruticosa (n=46), Haloxylon salicornicum (n=42) and Haloxylon recurvum (n=39) were said to be most effective against the infestations with gastrointestinal parasites. Aerial parts (43%), leaves (26%), fruits (9%), seeds and seed oils (9%) were the plant parts frequently used for preparation of remedies, while flowers, roots, bulbs and pods were less frequently used (<5%). Common preparations were decoction, jaggery and ball drench; oral drug administration was very common. There was some variation in the doses used for different animal species depending on age, size and physical condition of the animal and severity of the disease. In a second step the regionally most prevalent gastrointestinal parasites of sheep and goats were determined (Chapter 3) in 500 animals per species randomly chosen from pastoral herds across the previously studied five localities. Standard parasitological techniques were applied to identify the parasites in faecal samples manually collected at the rectum. Overall helminth prevalence was 78.1% across the 1000 animals; pure nematode infestations were most prevalent (37.5%), followed by pure trematode (7.9%), pure cestode (2.6%) and pure protozoa infestations (0.8%). Mixed infestations with nematodes and trematodes occurred in 6.4% of all animals, mixed nematode-cestode infestations in 3.8%, and all three groups were found in 19.1% of the sheep and goats. In goats more males (81.1%) than females (77.0%) were infested, the opposite was found in sheep (73.6% males, 79.5% females). Parasites were especially prevalent in suckling goats (85.2%) and sheep (88.5%) and to a lesser extent in young (goats 80.6%, sheep 79.3%) and adult animals (goats 72.8%, sheep 73.8%). Haemonchus contortus, Trichuris ovis and Paramphistomum cervi were the most prevalent helminths. In a third step the in vitro anthelmintic activity of C. decidua, S. foetida, S. fruticosa, H. salicornicum and H. recurvum (Chapter 2) was investigated against adult worms of H. contortus, T. ovis and P. cervi (Chapter 3) via adult motility assay (Chapter 4). Various concentrations ranging from 7.8 to 500 mg dry matter/ml of three types of extracts of each plant, i.e. aqueous, methanol, and aqueous-methanol (30:70), were used at different time intervals to access their anthelmintic activity. Levamisol (0.55 mg/ml) and oxyclozanide (30 mg/ml) served as positive and phosphate-buffered saline as negative control. All extracts exhibited minimum and maximum activity at 2 h and 12 h after parasite exposure; the 500 mg/ml extract concentrations were most effective. Plant species (P<0.05), extract type (P<0.01), parasite species (P<0.01), extract concentration (P<0.01), time of exposure (P<0.01) and their interactions (P<0.01) had significant effects on the number of immobile/dead helminths. From the comparison of LC50 values it appeared that the aqueous extract of C. decidua was more potent against H. contortus and T. ovis, while the aqueous extract of S. foetida was effective against P. cervi. The methanol extracts of H. recurvum were most potent against all three types of parasites, and its aqueous-methanol extract was also very effective against T. ovis and P. cervi. Based on these result it is concluded that the aqueous extract of C. decidua, as well as the methanol and aqueous-methanol extract of H. recurvum have the potential to be developed into plant-based drugs for treatment against H. contortus, T. ovis and P. cervi infestations. Further studies are now needed to investigate the in vivo anthelmintic activity of these plants and plant extracts, respectively, in order to develop effective, cheap and locally available anthelmintics for pastoralists in Cholistan and neighboring desert regions. This will allow developing tangible recommendations for plant-based anthelminthic treatment of sheep and goat herds, and by this enable pastoralists to maintain healthy and productive flocks at low costs and probably even manufacture herbal drugs for marketing on a regional scale.

Factores que influyen en los comportamientos sexuales de prevención frente al virus de inmunideficiencia humana (VIH) en los adictos a las drogas por vía parenteral (ADVP)

Los datos existentes sobre el progresivo incremento de la infección con el virus de inmunodeficiencia humana (VIH) entre los adictos a las drogas por via parenteral (ADVP) y sus parejas e hijos, plantean la necesidad urgente de elaborar programas preventivos con el mayor grado de eficacia posible. En el presente trabajo nos proponemos tres objetivos: 1) Poner de manifiesto algunas insuficiencias observadas en los modelos deprevención que se aplican al caso del SIDA. 2) Conferir un énfasis especial a la influencia sobre los comportamientos preventivos frente al SIDA, de ciertos factores que, en general, no se tienen 10 bastante en cuenta en los modelos actuales como son: la magnitud del reforzamiento contingente a un determinado comportamiento y la demora con la que éste se recibe. 3) Exponer los resultados de una investigación realizada con drogadictos por via parenteral (Planes, 1991), cuyos objetivos eran conocer las relaciones existentes entre la magnitud y la demora del reforzamiento contingente a los comportamientos sexuales preventivos y la frecuencia de dichos comportamientos

Tecnología médica : mitos y realidades

No todo tiempo pasado fue mejor. Descubrimientos médicos invaluables, un amplio portafolio de medicamentos y una inigualable dotación de equipos hacen que, en la actualidad, las alternativas para los pacientes sean más y mejores. La época en que los médicos se quedaban sin respuesta ante los enigmas de la salud ya es historia. Este disfrute de una medicina más certera se debe, en gran medida, a la ingeniería biomédica o bioingeniería, una ciencia que ha revolucionado al mundo. Gracias a ella, la humanidad ha sido testigo de magnánimos descubrimientos como el radio (elemento químico desarrollado por los esposos Curie), los rayos X (Roentgen) y el electrocardiógrafo (utilizado por primera vez en 1903 por Einthoven). Es tal el despliegue de tecnología que, de acuerdo con la Food and Drug Administration (FDA), organismo de los Estados Unidos que se encarga del registro, control y certificación de los dispositivos médicos, hoy en día existen más de 100 mil tipos de equipos médicos, sin olvidar que cada año se agregan a este arsenal 5 mil nuevos. Si bien este panorama luce como un triunfo para la humanidad, expertos aseguran que nada es tan perfecto como parece y que, en cambio, la tecnología médica tiene sus puntos en contra, sus mitos y realidades. Aunque no cabe la menor duda de que la tecnología médica ha contribuido a solucionar cientos de problemas de la humanidad y que ha ofrecido un sinnúmero de respuestas a las más grandes incógnitas, tampoco se puede ocultar que este mar de opciones no resulta tan benéfico, pues adquirir la tecnología adecuada, entre tanta diversidad, es un verdadero problema para los sistemas de salud, sobre todo si se tiene en cuenta que no todos los equipos son ciento por ciento seguros. El tema de los eventos adversos que presentan los dispositivos médicos no es nuevo. En 1970, Ralph Nader (activista y abogado estadounidense) denunció que alrededor de unos 1.200 norteamericanos podían ser electrocutados, cada año, por procedimientos rutinarios de diagnóstico y terapia (Nader, 1970, 176-179). Un año más tarde, el Instituto para la Investigación del Cuidado de Emergencia (ECRI, por sus siglas en inglés) emitió un reporte contundente: “una perturbadora cantidad de equipos médicos han demostrado ser inefectivos, peligrosos y de mala calidad” (Emergency Care Research Institute, 1971, 75-93). Más adelante, el Instituto Nacional de Medicina de los Estados Unidos encontró que alrededor de 44 mil a 98 mil norteamericanos mueren anualmente debido a errores médicos, situación que se da porque “el uso de tecnologías, cada vez más sofisticadas y complejas, es un factor contribuyente a la cantidad de errores encontrados” (Committee on Quality Health Care in America, 2000). Entonces, ¿esto se traduce en que la industria médica es insegura? Sí. Tal vez la menos segura de todas. Literalmente hablando, se puede decir que es mejor vivir al lado de una planta nuclear que entrar a un hospital. Una conclusión que, aunque perturbadora, es real. Así lo prueban los análisis que se hacen sobre niveles de “peligrosidad” (ver imagen) y en los cuales se registran la cantidad de vidas que se pierden por año (eje horizontal) versus la cantidad de sucesos ocurridos por instalación (eje vertical).

Soluciones isotónicas versus hipotónicas como líquidos de mantenimiento en niños en estado crítico

El desarrollo de hiponatremia aguda en los pacientes hospitalizados se ha asociado con el uso de líquidos de mantenimiento hipotónicos.3,5-7,11-13,15-21 El propósito de este estudio es determinar si el uso de soluciones hipotónicas (60 meq/l Na) como líquidos de mantenimiento en niños críticos inducen más hiponatremia aguda que soluciones isotónicas (lactato ringer). Método: Se realizó un estudio retrospectivo de cohorte, que incluyó los niños que ingresaron a la UCIP de la Fundación Cardioinfantil desde septiembre de 2009 a diciembre de 2011 con edades entre 6 meses y 10 años, quienes requirieron líquidos endovenosos de mantenimiento con 60 meq/l de sodio o lactato Ringer. Resultados: En total se estudiaron 117 pacientes de los cuales 71 niños recibieron 60 meq/L de Na y 46 recibieron lactato Ringer, las características demográficas y clínicas fueron similares en ambos grupos. De los pacientes que recibieron 60 meq/L de sodio se encontró hiponatremia en un 28,1% ( n= 20) vs 17.4% ( n=8) de los que recibieron 130 meq /l sodio, sin observar diferencias significativas ( RR 1,863 IC95% 0,779- 4,680 p=0.1302) . Conclusiones: En niños críticos que requieren líquidos de mantenimiento no se encontraron diferencias en la frecuencia de aparición de hiponatremia sintomática inducidas por el tipo de solución utilizada. El lactato de Ringer y la Dextrosa con 60 mq/lit de sodio fueron seguros y efectivos para sostener el estado de hidratación.

The nature of Medicines

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Estrategias de internacionalización frente a los TLCs para la empresa Inversiones Sanco Ltda.

La realidad actual de las empresas colombianas, incluye un reto importante, los vigentes Tratados de Libre Comercio, que pueden convertirse en una amenaza u oportunidad para las empresas nacionales. Es por ello, que el presente documento, describe la investigación, resultados y recomendaciones consecuentes al programa de consultoría realizado junto al Centro de Innovación y Desarrollo Empresarial (CIDEM) de la Universidad del Rosario y sus consultores expertos, para apoyar y preparar Pequeñas y Medianas Empresas como Inversiones Sanco, a enfrentarse a las nuevas oportunidades de negocio, que representa el Tratado de Libre Comercio con Estados Unidos, a través de recomendaciones y planes de mejora que la empresa puede implementar y que buscan aumentar su nivel competitividad para enfrentarse a sus competidores nacionales y extranjeros.

Caracterización clínica, microbiológica y ecocardiográfica de pacientes con Endocarditis infecciosa en la Fundación Cardioinfantil 2002-2012

Introducción: La endocarditis infecciosa es una infección microbiana del endocardio poco estudiada en nuestro país, la cual se asocia con múltiples complicaciones clínicas, y que presenta una mortalidad importante, que no ha disminuido a lo largo del tiempo sin importar los cambios epidemiológicos, de tratamiento y el aumento de la cirugía valvular que se presentan en la actualidad. Metodología: Se realizó la búsqueda de los pacientes adultos con diagnóstico de endocarditis infecciosa entre los años 2002 a 2012 en la Fundación Cardioinfantil para la revisión de los registros médicos y la descripción de las características clínicas, microbiológicas y ecocardiográficas. Resultados: se detectaron 144 pacientes hallando un predominio de la lesión de válvula nativa y el compromiso de válvula aórtica, encontrando como germen más común el S. aureus, sin embargo una tasa de 32.6% de hemocultivos negativos. La mortalidad intrahospitalaria fue de 22.2%. Discusión: los datos hallados en general son semejantes a los descritos en la literatura mundial con excepción de algunas variables discordantes en cuanto a la válvula aórtica mayormente comprometida y factores asociados a la endocarditis tricuspidea. Conclusión: la epidemiología de la endocarditis infecciosa de nuestra serie es muy semejante a la de la literatura actual de los países industrializados, aunque con algunas excepciones, requiriéndose la implementación y profundización del estudio de esta patología a nivel nacional.