Aim: To determine the effects of cigarette smoke (CS) exposure on the expression/activation of mitogen-activated protein kinases (MAPKs) (extracellular signal-regulated kinase [ERK1/2], p38-kinase [p38] and c-Jun NH 2 -terminal protein kinase [JNK]), norepinephrine (NE) levels and myocardial structure and function. Methods: Rats were randomised to two groups: CS-exposed (n = 12) or room air (CON) (n = 10). After 5 weeks, the animals underwent echocardiography with pulse-wave Doppler flow measurements. Hearts were removed for microscopy and Western blot analysis. Results: CS exposure was associated with significant increases in NE urinary levels and larger ventricular dimensions (mm) (CON = left ventricular end diastolic dimension [LVEDD] 7.99 ± 0.10, LV end systolic dimension [LVESD] 4.55 ± 0.20, CS = LVEDD 8.3 ± 0.10, LVESD 5.3 ± 0.09, p = 0.026, p = 0.003). There was also evidence of systolic dysfunction in the CS-exposed group compared to the CON group (fractional shortening %, CON = 43 ± 2, CS = 36 ± .09, p = 0.010). In CS-exposed hearts, significant increases in phosphorylated p38/total p38 (0.975 ± 0.05) and phosphorylated ERK1/2/totalERK1/2 (1.919 ± 0.050) were found compared to CON hearts (0.464 ± 0.008, 0.459 ± 0.050, respectively). No significant differences were found in JNK levels between the groups. Conclusions: Increased NE levels and MAPK activation are associated with CS-related left ventricular remodelling. Published by Elsevier B.V. on behalf of European Society of Cardiology.

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A non-enzymatic protocol for the purification of hemozoin, the malaria pigment, accumulated in the liver and spleen of mice infected with Plasmodium yoefii has been developed. The procedure, including repeated extraction with 2.5% SDS followed by washings with methanol, chloroform and bicarbonate buffer, completely removes the non-hemozoin heme and other non-covalently adhered biomolecules. The purified hemozoin contains 94-98% ferriprotoporphyrin IX as quantitated by spectral analysis. A parasitemia-dependent accumulation of hemozoin was demonstrated which was more marked in the liver than in the spleen.

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A stage-dependent increase in the level of putrescine, spermidine, and spermine during intraerythrocytic growth of Plasmodium knowlesi in rhesus monkey erythrocytes was observed. Further, intraerythrocytic P. knowlesi-induced putrescine influx was found in trophozoite stage-infected erythrocytes and process was time-and temperature-dependent and showed saturable kinetics. Characteristics of induced putrescine influx appears in infected erythrocytes to be close to the normal erythrocytes in terms of affinity of putrescine to the putrescine transporter (K m 34.6 ؎ 3.8 M as normal erythrocytes and K m 37.2 ؎ 5.2 M in infected erythrocytes). However, the difference involves the significant increase in the putrescine influx rate after infection (V max ‫؍‬ 4.21 nmol/min/10 10 normal erythrocytes, compared with 11.6 nmol/min/10 10 infected erythrocytes). Energy dependence, involvement of -SH group, and noninterference by amino acid, spermidine, and spermine in the putrescine influx process clearly demonstrate the presence of a distinct transporter for putrescine in infected erythrocytes. A putrescine conjugate N 1 ,N 4 -bis-(7-chloroquinoline-4-yl)butane-1,4-diamine (BCBD) was synthesized, which inhibits the putrescine influx in the P. knowlesi infected erythrocytes (K i of 43.2 M) as well as in vitro growth of P. knowlesi (IC 50 value, 7.64 ؎ 0.97 ng/ml BCBD, 10.8 ؎ 0.45 ng/ml chloroquine). Addition of exogenous polyamines failed to reverse the inhibitory effect of BCBD in vitro. Administration of BCBD (24 mg/kg body weight, intraperitoneal, twice a day for 4 days) cured the Swiss mice infected with multidrugresistant infection of Plasmodium yoelii. Therefore, inhibition of putrescine transport in malaria-infected erythrocytes offers a lead in the search of a new class of chemotherapeutic molecules against malaria.