Can Inconsistent Association between Hypertension and Cognition in Elders be Explained by Levels of Organochlorine Pesticides?

The relation between hypertension and cognition in elders remains unclear, and studies on the effect of antihypertensive drugs on cognition have demonstrated conflicting results. This study was performed to evaluate if the association between hypertension and cognition in elders differed depending on serum concentrations of organochlorine (OC) pesticides, common neurotoxic chemicals. Participants were 644 elders aged 60–85 years who participated in the National Health and Nutrition Examination Survey 1999–2002 and were able to complete a cognitive test. We selected 6 OC pesticides that were commonly detected in the elderly. Cognition was assessed by the Digit Symbol Substitution Test (DSST), a relevant tool for evaluating hypertension-related cognitive function, and low cognition was defined by the DSST score < 25^th percentile. When OC pesticides were not considered in the analyses, elders with hypertension had about 1.7 times higher risk of low cognition than those without hypertension. However, in analyses stratified by serum concentrations of OC pesticides, the associations between hypertension and low cognition were stronger the higher the serum concentrations of p,p’-DDT, p,p’-DDE, β-hexachlorocyclohexane, and trans-nonachlor increased. Among elders in the 3^rd tertile of these pesticides, adjusted odds ratios were from 2.5 to 3.5. In contrast, hypertension was not clearly associated with the risk of low cognition in elders in the 1^st tertile of these pesticides. Similar patterns were observed for the continuous DSST score dependent variable. The difference in the association between hypertension and DSST scores according to the levels of OC pesticides suggest a key role of OC pesticides in the development of hypertension-related cognitive impairment and may help to identify hypertensive elders who are at a high risk of cognitive impairment.     

Mutation of serine residue 318 in the class C β-lactamase of Enterobacter cloacae 908R

The involvement of the serine residue 318 in the specificity of a class C beta-lactamase was investigated. Multiple site-directed mutants at this position were generated using a polymerase chain reaction technique. These mutants were then probed for their activity towards various beta-lactam compounds. One mutant, S318G was further purified and its physico-chemical and catalytic properties determined. It was shown that the observed minimal inhibitory concentration values of this mutant could be correlated to its kinetic properties using a 'diffusion-hydrolysis' model. However, the data showed that residue 318 has little influence on the specificity of class C beta-lactamases.     

A multisensory integration model of human stance control

A model is presented to study and quantify the contribution of all available sensory information to human standing based on optimal estimation theory. In the model, delayed sensory information is integrated in such a way that a best estimate of body orientation is obtained. The model approach agrees with the present theory of the goal of human balance control. The model is not based on purely inverted pendulum body dynamics, but rather on a three-link segment model of a standing human on a movable support base. In addition, the model is non-linear and explicitly addresses the problem of multisensory integration and neural time delays. A predictive element is included in the controller to compensate for time delays, necessary to maintain erect body orientation. Model results of sensory perturbations on total body sway closely resemble experimental results. Despite internal and external perturbations, the controller is able to stabilise the model of an inherently unstable standing human with neural time delays of 100 ms. It is concluded, that the model is capable of studying and quantifying multisensory integration in human stance control. We aim to apply the model in (1) the design and development of prostheses and orthoses and (2) the diagnosis of neurological balance disorders. Received: 25 August 1997 / Accepted in revised form: 8 December 1998     

Cranial Suture Regeneration Mitigates Skull and Neurocognitive Defects in Craniosynostosis

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Lung protein leaks in ventilated lambs: effects of gestational age

To study the protein permeability properties of the ventilated premature lung, we delivered groups of eight lambs at 122 and 135 days gestational age and ventilated the lambs equivalently. The lambs at 122 days gestational age had been treated with natural sheep surfactant at birth, and both groups of lambs had similar pH and blood gas values to 3 h of age. Three groups of lambs at 146 days gestational age also were studied for comparison; four lambs were ventilated to normalized PCO2 values, four lambs were ventilated equivalently to the premature lambs with supplemental CO2 used to normalize PCO2 values, and four lambs were treated with natural surfactant and ventilated similarly to the preterm lambs. The percent recovery into an alveolar wash and lung tissue of 131I-albumin given by intravascular injection and of 125I-albumin given into the airways was measured in each animal after killing at 3 h of age. Full-term lambs had a small bidirectional leak of albumin to and from the alveoli and lung tissue. The recovery of intravascular 131I-albumin in the alveolar wash was 5.8- and 4.1-fold higher in lambs at 122 and 135 days gestational age, respectively, than in full-term lambs. The loss of 125I-albumin from the airways and alveoli also increased as gestational age decreased. The bidirectional flux of albumin to and from the alveoli increased as gestational age decreased in the prematurely delivered and ventilated lambs.     

Stability of o-phthalaldehyde-derived isoindoles

The degradation of 1-alkylthio-2-alkylisoindoles, generated in situ by reaction of o-phthalaldehyde with primary alkylamines in the presence of selected thiols, was studied under conditions typical of those used in precolumn derivatization applications. In all cases, loss of isoindole followed pseudo first order kinetics and was strongly accelerated by excess o-phthalaldehyde in the reaction mixture. Reactivity toward o-phthalaldehyde was found to be influenced by a number of experimental parameters including thiol structure, thiol concentration, amine structure, solvent composition, and pH. In the absence of excess o-phthalaldehyde, the stability of all derivatives examined was excellent. These results provide a basis for optimization of reaction conditions for maximum derivative stability.     

Total DNA synthesis and cloning in Escherichia coli of a gene coding for the human growth hormone releasing factor

A DNA containing a sequence coding for the human growth hormone releasing factor (hGRF) has been obtained by enzymatic assembly of chemically synthesized DNA fragments. The synthetic gene consists of a 140 base-pair fragment containing initiation and termination signals for translation and appropriate protruding ends for cloning into a newly constructed plasmid vector (pULB1219). Eleven oligodeoxyribonucleotides, from 14 to 31 bases in length, sharing pairwise stretches of complementary regions of at least 13 bases were prepared by phosphotriester solid-phase synthesis. The DNA sequence was designed to take into account the optimal use of E. coli codons. Oligomers were annealed in one step and assembled by ligation. The DNA fragment of the expected size (140 bp) was recovered and cloned into the pULB1219 vector. The expected sequence was confirmed by DNA sequencing.     

Quantal analysis indicates an alpha-toxin-like block by lophotoxin, a non-ionic marine natural product

The effects of a structurally novel paralytic substance (lophotoxin) on quantal transmission parameters and the time course of synaptic potentials have been examined. This substance completely abolished potentials by reducing quantal size without affecting the release of quanta. Nerve conduction, membrane potential, and the passive electrical properties of the muscle end-plate remained unaffected. Lophotoxin appears to act directly on the acetylcholine receptor-channel complex, although perhaps not the cholinoreceptive site itself, as suggested by the unusual chemistry and onset kinetics of this toxin.