Abstract Objectives To evaluate different types of perianal fistulas and their complications on magnetic resonance imaging (MRI) and to compare plain, contrast, and jelly magnetic resonance fistulography findings. Materials and Methods This prospective study was performed in 30 patients who presented with perianal pus discharge or external fistulous opening. Magnetic resonance imaging of the perianal region before and after giving intravenous contrast and after injecting jelly through a percutaneous opening was performed on a 3T scanner and the results were correlated. Results The mean age of the patients was 40.13±13.88 years (range 19-75 years). The male to female ratio was 14:1. The most common type of fistula was St. James classification type I, which was seen in 13 patients (43%), followed by type IV in 30%, type III in 16%, type II in 6.66%, and type V in 3.33% of the patients. Using agreement analysis, we compared the number of primary and secondary tracts, internal openings, and horseshoe tracts and found a significant agreement between plain and post Jelly MRI fistulography (kappa statistic close to 1).When comparing plain and contrast MRI, there was significant agreement in the primary and secondary tracts, while statistically insignificant results were obtained (p>0.05) for the horseshoe tract and internal openings. Contrast injection was helpful in 7 subjects (23.3%) as peripheral enhancement of abscesses were better delineated. Conclusion Magnetic resonance imaging is the one stop diagnostic modality for perianal fistulas. Acquisition of axial (Ax) T2, axial T2 FS, coronal T2 and coronal T2 FS sequences without administering intravenous contrast or jelly is usually sufficient for the diagnosis of fistulas and their complications.

ABSTRACT Background: Tretinoin and 5-fluorouracil are indicated for treatment of various skin disorders and actinic keratosis respectively. Objective: Present study was focused to design liposomes containing 5- fluorouracil and tretinoin. Design was further optimized by 32 full factorial design. Methods: Liposomes were prepared by ethanol injection method and evaluated by Transmission Electron Microscopy, percentage entrapment efficiency, zeta potential and in vitro drug release. Optimized formulation was subjected to histopathological and stability studies at 4ºC, 25ºC and 60ºC temperatures. Results: No drug crystals were visible in transmission electron microscopy, regardless of the preparation technique or the loaded drug. Formulation F9 showed maximum drug entrapment of 72.86% and 69.70% for 5-fluorouraciland tretinoin respectively. When phospholipid concentration was increased from 40 to 60 mg/ml, encapsulation efficiencies of formulation increased. Zeta potential and particle size were maintained within range of -19.14 to -25.61 and 100 to 200 nm respectively which facilitated good stability and penetration of liposomes. Dissolution profiles of formulations F1 to F6 showed high amount of drug release (30.6 to 67.42%) at 2 h. Liposomes were not stable at high temperature but formulations were most stable when stored at lower temperature i.e. 4oC. Conclusion: So, in liposomes both 5-fluorouracil and tretinoin were successfully incorporated and it can be further used for formulation development.

RESUMEN Objetivo: El presente estudio se centró en el diseño de liposomas que contenían 5-fluorouracilo y tretinoína. El diseño fue optimizado por 32 diseño factorial completo. Metodos: Los liposomas se prepararon mediante el método de inyección de etanol y se evaluaron mediante Microscopía Electrónica de Transmisión, % de eficiencia de encapsulación, potencial zeta y liberación de fármaco in vitro. La formulación optimizada se sometió a estudios histopatológicos y de estabilidad a temperaturas de 4ºC, 25ºC y 60ºC. Resultados: Ningún cristal de los fármacos era visibles en el Microscopía Electrónica de Transmisión, sin importar la técnica de la preparación o el fármaco cargado. La formulación F9 demostró el atrapamiento máximo del fármaco del 72,86% y del 69,70% para 5-fluorouracilo y tretinoína respectivamente. Cuando la concentración del fosfolípido fue aumentada a partir de 40 a 60 mg/ml, las eficiencias de encapsulación de la formulación aumentaron. El potencial de zeta y el tamaño de partícula fueron mantenidos dentro de la gama de-19,14 a -25,61 y 100 a 200 nanómetros respectivamente, que facilitó la buena estabilidad y la penetración de liposomas. Los perfiles de disolución de las formulaciones F1 a F6 mostraron una alta cantidad de liberación de fármaco (30,6 a 67,42%) a las 2h. Los liposomas no eran estables a alta temperatura, pero las formulaciones eran más estables cuando se almacenaban a una temperatura más baja, es decir, 4 ºC. Conclusiones: Así, en los liposomas, tanto los fármacos 5-fluorouracilo como los tretinoína se incorporaron con éxito y se pueden utilizar para el desarrollo de la formulación.

O trabalho teve como objetivo o desenvolvimento de novas cápsulas com revestimento entérico HPMC (ECHC) conectadas com microesponjas carregadas com fluoruracila (5-FU) em combinação com grânuos de pectinato de cálcio. O método de difusão de solvente modificado quasi-emulsão foi usado para formular microesponjas com base no planejamento fatorial 32 e determinaram-se os efeitos das variáveis independentes (volume de solvente orgânico e conteúdo Eudragit RS100) sobre as variáveis dependentes (tamanho de partícula, EE% e % CDR). As microesponjas otimizadas (F4) foram caracterizadas por SEM, PXRD, TGA e ligadas aos grânulos de pectinato de cálcio em cápsulas de HPMC e estas foram, ainda, revestidas com polímero entérico Eudragit L 100 (Ed-L100) e/ou Eudrgit S 100 (Ed S 100) em diferentes proporções. No estudo de liberação in vitro de ECHC foi realizada em vários meios de liberação sequencial SGF durante 2 h, seguido de SIF para as próximas 6 h, e, em seguida, em SCF (na presença e na ausência de enzima pectinase por mais 16 h). A liberação do fármaco foi retardada em revestimento com a EDS-100, em comparação com mistura de EDS-100: EDL-100, de revestimento. O percentual de 5-FU liberado de ECHC 3 ao final de 24 h foi 97,83 ± 0,12% em presença de pectinase, enquanto que para o controle foi de 40,08 ± 0,02% do fármaco. A formulação otimizada foi submetida a estudos Roentgenográficos in vivo, em coelhos brancos Nova Zelândia, para analisar o comportamento das cápsulas desenvolvidas direcionadas ao cólon. Os estudos de farmacocinética em coelhos brancos da Nova Zelândia foram conduzidos para determinar a extensão da exposição sistêmica propiciada pela formulação desenvolvida, em comparação com solução aquosa de 5-FU. Assim, cápsulas entéricas de HPMC revestidas e conectadas com microesponjas carregadas com 5-FU e grânulos de pectinato de cálcio se mostraram promissoras como formulação para liberação do fármaco no cólon no tratamento do câncer colorretal.

The work was aimed at developing novel enteric coated HPMC capsules (ECHC) plugged with 5 Florouracil (5-FU) loaded Microsponges in combination with calcium pectinate beads. Modified quasi-emulsion solvent diffusion method was used to formulate microsponges based on 32 factorial design and the effects of independent variables (volume of organic solvent and Eudragit RS100 content) on the dependent variables (Particle size, %EE & % CDR) were determined. The optimized microsponges (F4) were characterized by SEM, PXRD, TGA and were plugged along with calcium pectinate beads in HPMC capsules and the HPMC capsules were further coated with enteric polymer Eudragit L 100 (Ed-L100) and/ or Eudrgit S 100 (Ed-S 100) in different proportions. In vitro release study of ECHC was performed in various release media sequentially SGF for 2 h, followed by SIF for the next 6 h and then in SCF (in the presence and absence of pectinase enzyme for further 16 h). Drug release was retarded on coating with EdS-100 in comparison to blend of EdS-100: EdL-100 coating. The percentage of 5-FU released at the end of 24 h from ECHC 3 was 97.83 ± 0.12% in the presence of pectinase whereas in control study it was 40.08 ± 0.02% drug. The optimized formulation was subjected to in vivo Roentgenographic studies in New Zealand white rabbits to analyze the in vivo behavior of the developed colon targeted capsules. Pharmacokinetic studies in New Zealand white rabbits were conducted to determine the extent of systemic exposure provided by the developed formulation in comparison to 5-FU aqueous solutions. Thus, enteric coated HPMC capsules plugged with 5-FU loaded microsponges and calcium pectinate beads proved to be promising dosage form for colon targeted drug delivery to treat colorectal cancer.

OBJECTIVE: To describe India's National Antimalarial Drug Resistance Monitoring System, measure the efficacy of first-line malaria treatments, and determine risk factors for treatment failure. METHODS: In 2009-2010, prospective studies with 28 days of follow-up were conducted at 25 sentinel sites. Patients infected with Plasmodium falciparum were given artesunate plus sulfadoxine-pyrimethamine (AS+SP); those infected with P. vivax were given chloroquine. Polymerase chain reaction was used to distinguish post-treatment reinfection from treatment failure. Isolates of P. falciparum were checked for dhfr and dhps mutations. FINDINGS: Overall, 1664 patients were enrolled. Kaplan-Meier survival analysis showed an efficacy of 98.8% for AS+SP. Most patients with P. falciparum parasitaemia cleared their parasitaemias within 24 hours of treatment initiation, but six, including four with treatment failure, remained parasitaemic after 72 hours. Double mutants in dhfr were found in 68.4% of the genotyped isolates. Triple or quadruple mutants in dhfr and mutations in dhps were rare. A daily dose of artesunate of < 3 mg per kg of body weight, age of less than 5 years, and fever at enrolment were associated with an increased risk of treatment failure. Chloroquine remained 100% efficacious and generally cleared P. vivax parasitaemias within 48 hours. Vomiting (seen in 47 patients) was the most common adverse event. CONCLUSION: India's National Antimalarial Drug Resistance Monitoring System provides wide coverage. The first-line antimalarials used in the country remain safe and efficacious. The treatment of malaria in young children and the relative benefits of age- and weight-based dosing need further exploration.

OBJETIVO: Describir el sistema nacional de seguimiento de la resistencia a los fármacos contra el paludismo en India, medir la eficacia de los tratamientos de primera línea contra el paludismo y determinar los factores de riesgo en el fracaso del tratamiento. MÉTODOS: En los años 2009-2010, se llevaron a cabo estudios prospectivos con un seguimiento de 28 días en 25 sitios centinela. Se proporcionó artesunato con sulfadoxina-pirimetamina (AS+SP) a los pacientes infectados con Plasmodium falciparum, y cloroquina a los pacientes infectados con P. vivax . Se empleó la reacción en cadena de la polimerasa para distinguir la reinfección postratamiento del fracaso del tratamiento y se examinaron aislados de P. falciparum en busca de mutaciones de DHFR y DHPS. RESULTADOS: Se inscribieron un total de 1664 pacientes. Los análisis de supervivencia Kaplan-Meier mostraron una eficacia del 98,8% para el AS+SP. En la mayoría de pacientes con parasitemia por P. falciparum, ésta despareció en las 24 horas posteriores al inicio del tratamiento. Solo seis, incluidos los cuatro en los que el tratamiento fracasó, siguieron teniendo parasitemia pasadas 72 horas. Se encontraron mutantes dobles en DHFR en el 68,4% de los aislados genotipados. No fue frecuente encontrar mutantes en DHPS ni mutantes triples o cuádruples en DHFR. Una dosis diaria de artesunato de < 3 mg por kg de peso corporal, una edad inferior a 5 años y fiebre en el momento de la inscripción se asociaron con un riesgo superior de fracaso del tratamiento. La cloroquina fue eficaz en el 100% de los casos y eliminó, por lo general, las parasitemias por P. vivax en un plazo de 48 horas. El acontecimiento adverso más frecuente fueron los vómitos (presentes en 47 pacientes). CONCLUSIÓN: El sistema nacional de seguimiento de la resistencia a los fármacos contra el paludismo en India proporciona una cobertura amplia. Los fármacos antipalúdicos empleados en primera línea en el país continúan siendo seguros y eficaces. Se debe seguir examinando el tratamiento del paludismo en los niños pequeños y las ventajas relativas de la edad y las dosis basadas en el peso corporal.

OBJECTIF: Décrire le système national indien de surveillance de la résistance aux médicaments antipaludiques, mesurer l'efficacité des traitements antipaludiques de première ligne et déterminer les facteurs de risque de l'échec du traitement. MÉTHODES: En 2009-2010, des études prospectives, avec 28 jours de suivi, ont été menées dans 25 sites sentinelles. On a administré aux patients infectés par le Plasmodium falciparum de l'artésunate et de la sulfadoxine-pyriméthamine (AS+SP). Ceux qui étaient infectés par le P. vivax ont reçu de la chloroquine. La réaction en chaîne par polymérase a été utilisée pour distinguer la réinfection après traitement de l'échec du traitement. Des isolats de P. falciparum ont été vérifiés pour déceler les mutations de dhfr et de dhps. RÉSULTATS: Un total de 1664 patients ont participé à l'étude. L'analyse de survie de Kaplan-Meier a montré une efficacité de 98,8% de l'AS+SP. La plupart des patients infectés par le P. falciparum ont vu disparaître leurs parasitémies dans les 24 heures suivant le début du traitement, mais 6, dont 4 avec échec du traitement, sont restés parasitémiques après 72 heures. Des doubles mutations de dhfr ont été trouvées dans 68,4% des isolats génotypés. Les triples ou quadruples mutations de dhfr et les mutations de dhps étaient rares. Une dose quotidienne d'artésunate inférieure à 3 mg par kg de poids corporel, un âge inférieur à 5 ans, et de la fièvre au moment de l'enregistrement ont été associés à un risque accru d'échec thérapeutique. La chloroquine restait efficace à 100% et faisait généralement disparaître les parasitémies de P. vivax dans les 48 heures. Les vomissements (observés chez 47 patients) étaient l'effet indésirable le plus fréquent. CONCLUSION: En Inde, le système national de surveillance de la résistance aux médicaments antipaludiques offre une large couverture. Les antipaludéens de première ligne utilisés dans le pays restent sûrs et efficaces. Le traitement du paludisme chez les jeunes enfants et les avantages relatifs de la posologie en fonction de l'âge et du poids nécessitent une étude plus poussée.