The design, synthesis, and evaluation of organ-specific iron chelators. (57/239)

A series of iron chelators, three (S)-4,5-dihydro-2-(2-hydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid (DADFT) and three (S)-4,5-dihydro-2-(2-hydroxyphenyl)-4-thiazolecarboxylic acid (DADMDFT) analogues are synthesized and assessed for their lipophilicity (log Papp), iron-clearing efficiency (ICE) in rodents and iron-loaded primates (Cebus apella), toxicity in rodents, and organ distribution in rodents. The results lead to a number of generalizations useful in chelator design strategies. In rodents, while log Papp is a good predictor of a chelator's ICE, chelator liver concentration is a better tool. In primates, log Papp is a good predictor of ICE, but only when comparing structurally very similar chelators. There is a profound difference in toxicity between the DADMDFT and DADFT series: DADMDFTs are less toxic. Within the DADFT family of ligands, the more lipophilic ligands are generally more toxic. Lipophilicity can have a profound effect on ligand organ distribution, and ligands can thus be targeted to organs compromised in iron overload disease, for example, the heart.  (+info)

Comparison between the effects of dietary saturated (16:0), monounsaturated (18:1), and polyunsaturated (18:2) fatty acids on plasma lipoprotein metabolism in cebus and rhesus monkeys fed cholesterol-free diets. (58/239)

Cebus and rhesus monkeys were fed cholesterol-free diets providing 40% of energy as fat for 6-wk periods. The fats were high-linoleic acid safflower oil (HLSO), high-oleic acid safflower oil (HOSO), or palm oil (PO), rich in polyunsaturated (18:2), monounsaturated (18:1), or saturated (16:0) fatty acids, respectively. In cebus monkeys, plasma cholesterol concentrations during HLSO intake were 17-19% lower than those during HOSO or PO intake, attributed to a decrease in high-density lipoprotein (HDL). Plasma triglyceride (TG) and low-density-lipoprotein (LDL) cholesterol concentrations were comparable during all dietary treatments. Sixty-eight percent of total LDL catabolism was receptor mediated in all dietary groups and this was associated with similar apolipoprotein B pool sizes and fractional catabolic rates. Rhesus monkeys revealed similar cholesterol concentrations (total, LDL, and HDL) during all dietary treatments. TG concentrations during PO intake were 34% and 63% higher than those during HOSO and HLSO intakes, respectively. Hence, dietary 16:0 and 18:1 produce similar effects on LDL and HDL metabolism in normocholesterolemic primates.  (+info)

When size makes a difference: allometry, life-history and morphological evolution of capuchins (Cebus) and squirrels (Saimiri) monkeys (Cebinae, Platyrrhini). (59/239)

BACKGROUND: How are morphological evolution and developmental changes related? This rather old and intriguing question had a substantial boost after the 70s within the framework of heterochrony (changes in rates or timing of development) and nowadays has the potential to make another major leap forward through the combination of approaches: molecular biology, developmental experimentation, comparative systematic studies, geometric morphometrics and quantitative genetics. Here I take an integrated approach combining life-history comparative analyses, classical and geometric morphometrics applied to ontogenetic series to understand changes in size and shape which happen during the evolution of two New World Monkeys (NWM) sister genera. RESULTS: Cebus and Saimiri share the same basic allometric patterns in skull traits, a result robust to sexual and ontogenetic variation. If adults of both genera are compared in the same scale (discounting size differences) most differences are small and not statistically significant. These results are consistent using both approaches, classical and geometric Morphometrics. Cebus is a genus characterized by a number of peramorphic traits (adult-like) while Saimiri is a genus with paedomorphic (child like) traits. Yet, the whole clade Cebinae is characterized by a unique combination of very high pre-natal growth rates and relatively slow post-natal growth rates when compared to the rest of the NWM. Morphologically Cebinae can be considered paedomorphic in relation to the other NWM. Geometric morphometrics allows the precise separation of absolute size, shape variation associated with size (allometry), and shape variation non-associated with size. Interestingly, and despite the fact that they were extracted as independent factors (principal components), evolutionary allometry (those differences in allometric shape associated with intergeneric differences) and ontogenetic allometry (differences in allometric shape associated with ontogenetic variation within genus) are correlated within these two genera. Furthermore, morphological differences produced along these two axes are quite similar. Cebus and Saimiri are aligned along the same evolutionary allometry and have parallel ontogenetic allometry trajectories. CONCLUSION: The evolution of these two Platyrrhini monkeys is basically due to a size differentiation (and consequently to shape changes associated with size). Many life-history changes are correlated or may be the causal agents in such evolution, such as delayed on-set of reproduction in Cebus and larger neonates in Saimiri.  (+info)

The acetylcholinesterase inhibitor galantamine inhibits d-amphetamine-induced psychotic-like behavior in Cebus monkeys. (60/239)

Cholinergic receptors (AChR) are reported altered in brains from schizophrenic patients, and a growing body of evidence suggests that muscarinic receptor agonists exhibit antipsychotic potential. Centrally acting selective muscarinic receptor agonists are currently not available for clinical use, but acetylcholinesterase (AChE) inhibitors, which indirectly stimulate AChR by blocking the breakdown of acetylcholine by AChE, are widely used in the clinic against Alzheimer's disease. AChE inhibitors have been reported to exhibit antipsychotic efficacy in Alzheimer's disease patients, and these compounds have also been investigated as adjunctive treatment to antipsychotic medication in schizophrenic patients with varying results. However, monotherapy with AChE inhibitors in schizophrenic patients has not been evaluated. We wanted to investigate the antipsychotic potential of the AChE inhibitor galantamine, which also allosterically potentiates nicotinic receptor stimulation. To this end, we investigated its ability to antagonize d-amphetamine-induced psychotic-like behavior in extrapyramidal side effects (EPS)-primed Cebus monkeys. Galantamine inhibited d-amphetamine-induced unrest, arousal, and stereotypy. Side effects such as emesis, sedation, and EPS were minor or not existing. The results indicate that AChE inhibitors have antipsychotic potentials and suggest that clinical trials investigating antipsychotic effects of AChE inhibitors as monotherapy would be of interest.  (+info)

Exploring the relationship between cerebellar asymmetry and handedness in chimpanzees (Pan troglodytes) and capuchins (Cebus apella). (61/239)

A comparative study of chimpanzee (Pan troglodytes) and capuchin monkey (Cebus apella) cerebellar asymmetry and its relationship to handedness was conducted. Magnetic resonance images of the brain and behavioral data on a coordinated bimanual task were obtained from 16 chimpanzees and 11 capuchins. Chimpanzees displayed a greater rightward bias of the posterior cerebellum and capuchins displayed a greater leftward bias of the anterior cerebellum. Cerebellar asymmetries were significantly associated with handedness in capuchins but not chimpanzees, and this effect was most pronounced in right-handed capuchins.  (+info)

Cerebral petalias and their relationship to handedness in capuchin monkeys (Cebus apella). (62/239)

Cerebral asymmetries are thought to be associated with increased hemispheric specialization of function. We investigated cerebral petalias, the protrusion of one cerebral hemisphere relative to the other, and their relationship to lateralized behavior in capuchin monkeys (Cebus apella). Magnetic resonance images of the brain and behavioral data on a coordinated bimanual task were obtained from 13 capuchins. While a significant population-level left-frontal petalia was found, this was not related to handedness. The role of the morphologically asymmetric frontal cortex in capuchins is unclear, but may reflect developmental gradients or directional selection for various behavioral functions, such as extractive foraging or social group complexity.  (+info)

Impact of the 3,6,9-trioxadecyloxy group on desazadesferrithiocin analogue iron clearance and organ distribution. (63/239)

The impact of introducing a 3,6,9-trioxadecyloxyl group at various positions of the desazadesferrithiocin (DADFT) aromatic ring on iron clearance and organ distribution is described. Three DADFT polyethers are evaluated: (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolec arboxylic acid [(S)-4'-(HO)-DADFT-PE, 3], (S)-4,5-dihydro-2-[2-hydroxy-5-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolec arboxylic acid [(S)-5'-(HO)-DADFT-PE, 6], and (S)-4,5-dihydro-2-[2-hydroxy-3-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolec arboxylic acid [(S)-3'-(HO)-DADFT-PE, 9]. The iron-clearing efficiency (ICE) in rodents and primates is shown to be very sensitive to which positional isomer is evaluated, as is the organ distribution in rodents. The polyethers had uniformly higher ICEs than their corresponding parent ligands in rodents, consistent with in vivo ligand-serum albumin binding studies. Ligand 9 is the most active polyether analogue in rodents and is also very effective in primates, suggesting a higher index of success in humans. In addition, this analogue is also shown to clear more iron in the urine of the primates than many of the other chelators. If this trend were also observed in patients, it would facilitate iron-balance studies in a clinical setting.  (+info)

Do capuchin monkeys (Cebus apella) use tokens as symbols? (64/239)

In the absence of language, the comprehension of symbols is difficult to demonstrate. Tokens can be considered symbols since they arbitrarily stand for something else without having any iconic relation to their referent. We assessed whether capuchin monkeys (Cebus apella) can use tokens as symbols to represent and combine quantities. Our paradigm involved choices between various combinations of tokens A and B, worth one and three rewards, respectively. Pay-off maximization required the assessment of the value of each offer by (i) estimating token numerousness, (ii) representing what each token stands for and (iii) making simple computations. When one token B was presented against one to five tokens A (experiment 1), four out of ten capuchins relied on a flexible strategy that allowed to maximize their pay-off, i.e. they preferred one token B against one and two tokens A, and they preferred four or five tokens A against one token B. Moreover, when two tokens B were presented against three to six tokens A (experiment 2), two out of six capuchins performed summation over representation of quantities. These findings suggest that capuchins can use tokens as symbols to flexibly combine quantities.  (+info)