Estudios efectivos de potencial para algunas nuevas moléculas híbridas para su actividad contra el cáncer de próstata

Objective: The present work aimed at developing novel hybrid molecules for targeting the prostate cancer. It is observed that two human shock proteins Hsp70 and Hsp90 are over-expressed in prostate cancer making them one of the important drug targets. We have designed and developed twelve new hybrid molecules 6a-j for targeting these proteins. Methods: The designed molecules were prepared following a four step reaction protocol and characterized on the basis of proton NMR and Mass spectrometry. These were subjected to in vitro studies by means of Oncotest and CCK-8 assays with two cell lines DU145 and 22Rv1. The selected molecules 6b and 6i were subjected to molecular docking and then for SPR based affinity assay. Results: Compounds 6b and 6i were found to be highly active anticancer compounds comparable to standard drug enzalutamide. They have significant IC50 and high dock score for the Hsp70 and Hsp90. These compounds are selective and have good binding affinity for the Hsp70 due to high Kd. Conclusion: Compound 6b and 6i can serve as lead molecules for the development of antiprostate cancer drugs with Hsp70 as target.Objetivo: El presente trabajo tuvo como objetivo desarrollar nuevas moléculas híbridas para atacar el cáncer de próstata. Se observa que dos proteínas de choque humano, Hsp70 y Hsp90, se sobreexpresan en el cáncer de próstata, lo que las convierte en uno de los objetivos farmacológicos importantes. Hemos diseñado y desarrollado doce nuevas moléculas híbridas 6a-j para dirigir estas proteínas. Métodos: Las moléculas diseñadas se prepararon siguiendo un protocolo de reacción de cuatro etapas y se caracterizaron sobre la base de RMN de protón y espectrometría de masas. Estos se sometieron a estudios in vitro por medio de ensayos Oncotest y CCK-8 con dos líneas celulares DU145 y 22Rv1. Las moléculas seleccionadas 6b y 6i se sometieron a acoplamiento molecular y luego a ensayo de afinidad basado en SPR. Resultados: Se descubrió que los Compuestos 6b y 6i son compuestos anticancerígenos muy activos comparables al fármaco estándar enzalutamida. Tienen un IC50 significativo y una puntuación alta para el muelle de Hsp70 y Hsp90. Estos compuestos son selectivos y tienen una buena afinidad de unión por la Hsp70 debido a la alta Kd. Conclusión: Los compuestos 6b y 6i pueden servir como moléculas principales para el desarrollo de fármacos antiprostáticos contra el cáncer con Hsp70 como objetivo

Seasonal Movements, Migratory Behavior, and Site Fidelity of West Indian Manatees along the Atlantic Coast of the United States as Determined by Radio-telemetry

The study area encompassed the eastern coasts of Florida, Georgia, and South Carolina, including inland waterways such as the St. Johns River (Fig. 1). Manatees inhabited the relatively narrow band of water that lies between the barrier beaches and the mainland, occasionally venturing into the ocean close to shore. Between Miami and Fernandina Beach, Florida, 19 inlets provided manatees with corridors between the intracoastal waters and the Atlantic Ocean; the distance between adjacent inlets averaged 32 km(SD = 24 km) and varied from 3 to 88 km. Habitats used by manatees along this 900-km stretch ofcoastline varied widely and included estuaries, lagoons, rivers and creeks, shallow bays and sounds, and ocean inlets. Salinities in most areas were brackish, but ranged from completely fresh to completely marine. The predominant communities of aquatic vegetation also varied geographically and with salinity: seagrass meadows and mangrove swamps in brackish and marine waters along the southern half of peninsular Florida; salt marshes in northeastern Florida and Georgia; benthic macroalgae in estuarine and marine habitats; and a variety of submerged, floating, and emergent vegetation in freshwater rivers, canals, and streams throughout the region. Radio-telemetry has been used successfully to track manatees in other regions ofFlorida (Bengtson 1981, Powell and Rathbun 1984, Lefebvre and Frohlich 1986, Rathbun et al. 1990) and Georgia (Zoodsma 1991), but these early studies relied primarily on conventional VHF (very high frequency) transmitters and were limited in their spatial and temporal scope (see O'Shea and Kochman 1990 for overview). Typically, manatees were tagged at a thermal refuge in the winter and then tracked until the tag detached, usually sometime between the spring and fall of the same year. Our study differs from previous research on manatee movements in several important respects. First, we relied heavily on data from satellite-monitored transmitters using the Argos system, which yielded a substantially greater number of locations and more systematic collection of data compared to previous VHF tracking studies (Deutsch et al. 1998). Second, our tagging and tracking efforts encompassed the entire range of manatees along the Atlantic coast, from the Florida Keys to South Carolina, so inferences were not limited to a small geographic area. Third, we often used freshwater to lure manatees to capture sites, which allowed tagging in all months of the year; this provided more information about summer movement patterns than had previous studies which emphasized capture and tracking at winter aggregations. Finally, the study spanned a decade, and success in retagging animals and in replacing transmitters allowed long-term tracking ofmany individuals. This provided the opportunity to investigate variation in seasonal movements, migratory behavior, and site fidelity across years for individual manatees. (254 page document.

Estudios efectivos de potencial para algunas nuevas moléculas híbridas para su actividad contra el cáncer de próstata

Objective: The present work aimed at developing novel hybrid molecules for targeting the prostate cancer. It is observed that two human shock proteins Hsp70 and Hsp90 are over-expressed in prostate cancer making them one of the important drug targets. We have designed and developed twelve new hybrid molecules 6a-j for targeting these proteins. Methods: The designed molecules were prepared following a four step reaction protocol and characterized on the basis of proton NMR and Mass spectrometry. These were subjected to in vitro studies by means of Oncotest and CCK-8 assays with two cell lines DU145 and 22Rv1. The selected molecules 6b and 6i were subjected to molecular docking and then for SPR based affinity assay. Results: Compounds 6b and 6i were found to be highly active anticancer compounds comparable to standard drug enzalutamide. They have significant IC50 and high dock score for the Hsp70 and Hsp90. These compounds are selective and have good binding affinity for the Hsp70 due to high Kd. Conclusion: Compound 6b and 6i can serve as lead molecules for the development of antiprostate cancer drugs with Hsp70 as target.Objetivo: El presente trabajo tuvo como objetivo desarrollar nuevas moléculas híbridas para atacar el cáncer de próstata. Se observa que dos proteínas de choque humano, Hsp70 y Hsp90, se sobreexpresan en el cáncer de próstata, lo que las convierte en uno de los objetivos farmacológicos importantes. Hemos diseñado y desarrollado doce nuevas moléculas híbridas 6a-j para dirigir estas proteínas. Métodos: Las moléculas diseñadas se prepararon siguiendo un protocolo de reacción de cuatro etapas y se caracterizaron sobre la base de RMN de protón y espectrometría de masas. Estos se sometieron a estudios in vitro por medio de ensayos Oncotest y CCK-8 con dos líneas celulares DU145 y 22Rv1. Las moléculas seleccionadas 6b y 6i se sometieron a acoplamiento molecular y luego a ensayo de afinidad basado en SPR. Resultados: Se descubrió que los Compuestos 6b y 6i son compuestos anticancerígenos muy activos comparables al fármaco estándar enzalutamida. Tienen un IC50 significativo y una puntuación alta para el muelle de Hsp70 y Hsp90. Estos compuestos son selectivos y tienen una buena afinidad de unión por la Hsp70 debido a la alta Kd. Conclusión: Los compuestos 6b y 6i pueden servir como moléculas principales para el desarrollo de fármacos antiprostáticos contra el cáncer con Hsp70 como objetivo

STUDIES ON EFFECT OF FORMULATION AND PROCESSING PARAMETERS ON STABILITY OF KETOROLAC TROMETHAMINE ORALLY DISSOLVING FILMS

Objective: The objective of the proposed work was to study the effect of various formulation and process parameters of solvent casting method on the physical and chemical stability of Ketorolac Tromethamine (KT) in the orally dissolving film dosage form. Methods: KT-excipient interaction study was carried out both in solid state and by processing samples through the solvent casting technique. The samples were evaluated using IR spectroscopy (IR) and X-ray diffractometry (XRD). Solvent casting method was used to prepare KT films using different film-forming polymers, and solvents. The drying temperature and pH of the dispersion were also varied to study the effect of these parameters on the stability of KT. All the formulations were analysed chemically initially and after one month of storage at 40 °C/75% RH. Results: During KT-excipient interaction study in solid state KT was found to be stable. No significant changes were observed in its impurity profile. Interaction between different polymers and KT was observed after the solvent casting process as revealed by IR and XRD analysis. The interaction was further confirmed in the film formulations upon chemical analysis. The polymers showing interaction with KT in XRD and IR were making it unstable chemically and were responsible for its chemical degradation as revealed by chemical analysis. It was also revealed that KT is most stable when processed using water as the solvent. KT was found to be stable when processed at a higher temperature and at acidic pH during film formation. It was found that chemical stability is more when Polyethylene oxide (PEO) and water under acidic pH are used and films are dried at a higher temperature. Conclusion: Both formulation parameters and processing conditions of the solvent casting technique affects the stability of drugs and hence should be studied as part of pre-formulation studies while developing orally dissolving films of drugs

Total myocardial revascularization for situs inversus totalis with dextrocardia: a case report

We report our experience of two patients suffering from severe coronary artery disease and situs inversus totalis with dextrocardia. The surgeon, standing on the right side of the patients, performed coronary artery bypass grafting by harvesting the right internal mammary artery in lieu of the left one