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Four new potential agents muscarinic (allosteric modulators) were synthesized and studied by using the B3LYP density functional method. The optimum conformation and geometry structure of these compounds were determined and analyzed. Solvent effects were considered including a variable number (1-15) of explicit water molecules surrounding the compound in order to simulate the first hydration shell, as well as using the Tomasi's polarized continuum model (PCM). A similar simultaneous analysis of the potents W84 and DUO-3O allosteric modulator of muscarinic receptors was also carried out. The effect of the hydration on the total atomic charges and several intermolecular distances of interest were also discussed. The biological activity against acetylcholine of our four synthesized bispyridinium salts was determined. Relationships/tendencies structure-activity were established. Several general conclusions were underlined.

The effects on the geometry structure, atomic charges and vibrational wavenumbers of the main different substituents in the 5th position of the uracil ring were analysed, and relationships were established. The 5-monosubstituted derivatives studied were 5-XU (X=F, Cl, Br, I, CH(3), NH(2), NO(2)). The geometry and vibrational wavenumbers were determined in these molecules. The FT-IR and Raman spectra were studied with the support of B3LYP calculations using several basis sets. Several general conclusions were underlined., (Copyright 2010 Elsevier B.V. All rights reserved.)

Pituitary function has been shown to be regulated by an increasing number of factors, including cytokines and hormones, such as TNFalpha and T(3). Both the proinflammatory cytokine TNFalpha and T(3) have been suggested to be involved in the maintenance of tissue homeostasis in the anterior pituitary gland. In this report we show that T(3) negatively interferes with MAPK p38 and nuclear factor-kappaB (NF-kappaB) activation by TNFalpha in GH4C1 cells. Our data demonstrate that MAPK p38 is specifically activated upon exposure to TNFalpha and that T(3) abolishes this activation in a time-dependent manner by a mechanism that involves the induction of the MAPK phosphatase, DUSP1. Our data show that the pool of up-regulated DUSP1 by T(3) is mainly localized to the cytosol, and that TNFalpha does not affect this localization. On the other hand, we show that T(3) impairs the activation of the NF-kappaB pathway induced by TNFalpha, producing a significant decrease in NF-kappaB-dependent transcription, phosphorylation of IkappaBalpha, translocation of p65/NF-kappaB to the nucleus, and p65/NF-kappaB transactivation potential. Interestingly, the overexpression of DUSP1 inhibits the NF-kappaB activation achieved by either TNFalpha or ectopic expression of the upstream inducer of MAPK p38. Conversely, DUSP1 depletion abrogates the inhibitory effect of T(3) on the induction of NF-kappaB-dependent transcription by TNFalpha. Overall, our results indicate that T(3) antagonizes TNFalpha signaling in rat pituitary tumor cells through the induction of DUSP1.

Over the last 500 years, admixture among Amerindians, Europeans, and Africans, principally, has come to shape the present-day gene pool of Mexicans, particularly Mestizos, who represent about 93% of the total Mexican population. In this work, we analyze the genetic data of 13 combined DNA index system-short tandem repeats (CODIS-STRs) in 1,984 unrelated Mestizos representing 10 population samples from different regions of Mexico, namely North, West, Central, and Southeast. The analysis of molecular variance (AMOVA) test demonstrated low but significant differentiation among Mestizos from different regions (F(ST) = 0.34%; P = 0.0000). Although the spatial analysis of molecular variance (SAMOVA) predicted clustering Mestizo populations into four well-delimited groups, the main differentiation was observed between Northwest when compared with Central and Southeast regions. In addition, we included analysis of individuals of Amerindian (Purepechas), European (Huelva, Spain), and African (Fang) origin. Thus, STRUCTURE analysis was performed identifying three well-differentiated ancestral populations (k = 3). STRUCTURE results and admixture estimations by means of LEADMIX software in Mestizo populations demonstrated genetic heterogeneity or asymmetric admixture throughout Mexico, displaying an increasing North-to-South gradient of Amerindian ancestry, and vice versa regarding the European component. Interestingly, this distribution of Amerindian ancestry roughly reflects pre-Hispanic Native-population density, particularly toward the Mesoamerican area. The forensic, epidemiological, and evolutionary implications of these findings are discussed herein.

Objective: The aim of the present study was to evaluate the quality of integrated child health care management (ICHCM) promoted by the World Health Organization (WHO) after an in-service training course., Methods: The training was carried out in a rural and an urban health unit and in the paediatric ward of the local reference hospital. Tutorial courses were given to small groups (4-6 students) over a 5-day period (40 h in total). The courses consisted of demonstrations, discussions, analyses, applications and evaluations of the ICHCM (in-service training). The training was evaluated by comparing the quality of ICHCM given by each physician in their work place on three different occasions: 15 days before the course began (pre-course evaluation), 15 days after the course (post-course evaluation) and 6 months after the course had ended (follow-up evaluation). Each physician was observed in each period during his or her consultation with a child under 5 years of age who presented with acute diarrhoea or acute respiratory infection. A series of possible behaviours by physicians was checked against a list of behaviours that would indicate effective training., Results: The average grades obtained by the 24 physicians evaluated (pre- and post-course) increased from 74.5 to 96.6 (22.1 points, P < 0.01). Physicians whose baseline grade was <80 had the greatest increases. Their averages grades increased from 68.2 to 91.3 (23.1 points, P < 0.001). The overall change for the whole group was sustained for up to 6 months (post-course 96.6 points and follow-up 90.9 points, P > 0.05)., Conclusion: The quality of ICHCM improved after the in-service training. No additional resources were necessary in the clinical units. This type of training can be extended to other countries or health programmes.

Geometry, vibrational frequencies, atomic charges and several thermodynamic parameters (the total energy, the zero point energy, the rotational constants and the room temperature entropy) were calculated using ab initio quantum chemical methods for 2,3-difluorobenzonitrile molecule. The results were compared with experimental values. With the help of two specific scaling procedures, observed FTIR and Raman vibrational frequencies were analysed and assigned to different normal modes of the molecule. The error obtained was in general very low. Other general conclusions have also been deduced.

Raman spectrum of 2,4-dichlorobenzonitrile (2,4-DCBN) in powder form has been recorded in the region 50-4000 cm(-1) on a Jasco K-500 Raman spectrophotometer using the 488.0 nm radiation from an argon laser. FTIR spectra in the region 200-4000 cm(-1) have been recorded in KBr pellet and nujol mull on a Nicolet DX spectrometer. Using the observed Raman and IR frequencies, normal co-ordinate analysis has been carried out to support the vibrational analysis and to determine the planar and non-planar force fields.

Five monocyclic 4-benzoyl-4-phenyl-beta-lactam derivatives in carbon tetrachloride solutions were studied by FTIR spectroscopy. The Fourier self-deconvolution method was applied to enhance the resolution of the FTIR spectra. The calculated spectra of these five compounds, which were obtained by quantum mechanical methods, were compared with FTIR data. A complete assignment of the vibrational frequencies in the 4000-400 cm(-1) range was made. Several vibrations were selected as being useful to characterize the beta-lactam ring. Substituents on N1 (p-methoxyphenyl) and C3 (methyl, phenyl, maleimidyl, and phthalimidyl) on the beta-lactam ring increase the amide resonance and the planarity of the ring. The optimized geometry along with the total electric charges on the four atoms of the ring support an antibiotic action mechanism by a nucleophilic attack of the enzymes on the carbonyl carbon atom of the beta-lactam ring., (Copyright 2001 John Wiley & Sons, Inc. Biopolymers (Biospectroscopy) 62: 278-294, 2001)