Antimycobacterial And Cytotoxicity Activities Of Free And Liposome-encapsulated 3-(4'-bromo[1,1'-biphenyl-4-yl)-3-(4-bromo-phenyl)-n,n- Dimethyl-2-propen-1-amine

The antimycobacterial activity of 3-(4'-bromo[1,1'-biphenyl-4-yl)-3-(4- bromo-phenyl)-N,N-dimethyl-2-propen-1-amine (BBAP), free or incorporated in preformed liposomes, on extracellular M. tuberculosis H37Rv was 8 and 25 μM (MIC), respectively. Extracellular antimycobacterial activity was not significantly improved by entrapment of BBAP in liposomes, but there was a 6.1-fold reduction of BBAP cytotoxicity on J774 macrophages. Liposomal BBAP or its free form showed IC50 values of 165 and 27 μM, resulting in a selectivity index (SI=IC50/MIC) of 3.4 and 6.6, respectively. Free BBAP in concentrations from 10 to 80 μM were quite effective in eliminating intracellular M. tuberculosis while liposomal formulation was less effective at these concentrations.334871874Corbett, E.L., Watt, C.J., Walker, N., Mayer, D.B.M., Willians, B.G., Raviglione, M.C., Dye, C., (2003) Arch. Intern. Med., 163, p. 1009Vynnycky, E., Fine, P.E., (1997) Epidemiol. Infec., 119, p. 183Pandey, R., Khuller, G.K., (2005) J. Antimicrob. Chemother., 55, p. 430De Souza, A.O., Aily D., C.G., Sato, D.N., Durán, N., (1998) J. Antimicrob. Chemother., 42, p. 407De Souza, A.O., Junior, R.R.S., Ferreira-Julio, J.F., Rodriguez, J.A., Melo, P.S., Haun, M., Sato, D.N., Durán, N., (2001) Eur. J. Med. Chem., 36, p. 843De Souza, A.O., Pereira, D.G., Durán, N., (2002) Ann. Rev. Biomed. Sci., 4, p. 53De Souza, A.O., Hemerly, F.P., Busollo, A.C., Melo, P.S., Machado, G.M.C., Miranda, C.C., Santa-Rita, R.M., Durán, N., (2002) J. Antimicrob. Chemother., 50, p. 629De Souza, A.O., Santos, R.R., Sato, D.N., De Azevedo, M.M.M., Ferreira, D.A., Melo, P.S., Haun, M., Durán, N., (2004) J. Braz. Chem. Soc., 15, p. 682De Souza, A.O., Alderete, J.B., Faljoni-Alario, A., Silva, C.L., Durán, N., (2005) J. Chil. Chem. Soc., 50, p. 591De Conti, R., Gimenez, S.M.M., Haun, M., Pilli, R.A., De Castro, S.L., Durán, N., (1996) Eur. J. Med. Chem., 31, p. 915Bangham, A.D., Standish, M.M., Watkins, J.C., (1965) J. Mol. Biol., 13, p. 238Chen, P.S., Toribara, T.Y., Warner, H., (1956) Anal. Chem., 28, p. 1756Oh, Y.K., Nix, D.E., Straubinger, R.M., (1995) Antimicrob. Agents Chemother., 39, p. 2104Collins, L.A., Franzblau, S.G., (1997) Antimicrob. Agents Chemother., 41, p. 1004Denizot, F., Lang, R., (1986) J. Immun. Methods, 89, p. 27

Beneficial effects of the ethanol extract of Caesalpinia pyramidalis on the inflammatory response and abdominal hyperalgesia in rats with acute pancreatitis

AbstractEthnopharmacological relevanceCaesalpinia pyramidalis Tul. (Fabaceae) is a plant found in the Northeast of Brazil that is popularly used to treat inflammation. Acute pancreatitis (AP) is an inflammatory disease for which abdominal pain is a relevant symptom. As there is no specific therapy for AP, we investigated the effect of the ethanol extract from the inner bark of C. pyramidalis (EECp) on the AP induced by common bile duct obstruction (CBDO) in rats.Material and methodsAP was induced in male Wistar rats (200–250g, n=6–8) through laparotomy and subsequent CBDO. Animals were euthanized after 6 (G6h) or 24h (G24h) of induction. In the G6h protocol, animals were pretreated with EECp (100–400mg/kg, p.o.) or vehicle (Tween 80; 0.2%) 1h before CBDO or sham surgery. For the G24h protocol, rats were pretreated with EECp (400mg/kg, 1h before CBDO or 1h before and 12h after CBDO) or vehicle. The following parameters were measured: inflammatory/oxidative (myeloperoxidase activity and malondialdehyde formation in the pancreas and lung, leukocyte counts in the blood and serum nitrate/nitrite), enzymatic (serum amylase and lipase levels) and nociceptive (abdominal hyperalgesia).ResultsInduction of AP by CBDO significantly increased all the parameters evaluated in both G6h and G24h protocols when compared with the respective sham group. In the G6h protocol, the EECp pretreatment (400mg/kg) significantly reduced all these parameters, besides completely inhibiting abdominal hyperalgesia. The same profile of reduction was observed from two administrations of EECp in the G24h protocol, while one single dose of EECp was able to significantly reduce pancreatic MDA, serum lipase levels, leukocyte counts in the blood and abdominal hyperalgesia without affecting the other parameters in the G24h protocol. Furthermore, rutin was found in the EECp.ConclusionsOur results demonstrated that EECp decreases inflammation, lipoperoxidation and hyperalgesia in CBDO-induced AP, making it of interest in future approaches to treat this condition

New and conventional strategies for lung recruitment in acute respiratory distress syndrome

Mechanical ventilation is a supportive and life saving therapy in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Despite advances in critical care, mortality remains high. During the last decade, the fact that mechanical ventilation can produce morphologic and physiologic alterations in the lungs has been recognized. In this context, the use of low tidal volumes (VT) and limited inspiratory plateau pressure (Pplat) has been proposed when mechanically ventilating the lungs of patients with ALI/ARDS, to prevent lung as well as distal organ injury. However, the reduction in VT may result in alveolar derecruitment, cyclic opening and closing of atelectatic alveoli and distal small airways leading to ventilator-induced lung injury (VILI) if inadequate low positive end-expiratory pressure (PEEP) is applied. On the other hand, high PEEP levels may be associated with excessive lung parenchyma stress and strain and negative hemodynamic effects, resulting in systemic organ injury. Therefore, lung recruitment maneuvers have been proposed and used to open up collapsed lung, while PEEP counteracts alveolar derecruitment due to low VT ventilatio