On the Rotational Analysis of the Ground Vibrational State of CH3D Molecule

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models have been developed using comparative molecular field analysis (CoMFA) on a large data set (118 compounds) of diverse cyclic urea derivatives as protease inhibitors against the human immunodeficiency virus type 1 (HIV-1). X-ray crystal structures of HIV-1 protease bound with this class of inhibitors were used to derive the most probable bioactive conformations of the inhibitors. The enzyme active site was used as a constraint to limit the number of possible conformations that are sterically accessible. The test sets have been created keeping in mind structural diversity as well as the uniform simple statistical criteria (mean, standard deviation, high and low values) of the protease inhibitory activities of the molecules compared to the training sets. Multiple predictive models have been developed with the training sets (93 compounds in each set) and validated with the corresponding test sets (25 compounds in each set). All the models yielded high predictive correlation coefficients (q2 from 0.699 to 0.727), substantially high fitted correlation coefficients (r2 from 0.965 to 0.973), and reasonably low standard errors of estimates (S from 0. 239 to 0.265). The steric and electrostatic effects have approximately equal contributions, 45% and 55% (approximately), respectively, toward explaining protease inhibitory activities. This analysis yielded models with significant information on steric and electrostatic interactions clearly discerned by the respective coefficient contour plots when overlapped on the X-ray structure of the HIV-1 protease. The HINT CoMFA study revealed significant contribution of hydrophobicity toward protease inhibitory activity. The 3D visualization technique utilizing these contour plots as well as the receptor site geometry may significantly improve our understanding of the inhibitor-protease (HIV-1) interactions and help in designing compounds with improved activity.     

Low-power radio telemetry: the potential for remote patient monitoring

Radio-based signalling devices will play an important role in future generations of remote patient monitoring equipment, both at home and in hospital. Ultimately, it will be possible to sample vital signs from patients, whatever their location and without them necessarily being aware that a measurement is being taken. This paper reviews current methods for the transmission by radio of physiological parameters over ranges of 0.3, 3 and 30 m, and describes the radiofrequency hardware required and the carrier frequencies commonly used. Future developments, including full duplex systems and the use of more advanced modulation schemes, are described. The paper concludes with a case study of a human temperature telemeter built to indicate ovulation. Clinical results clearly show the advantage to be had in adopting radio biotelemetry in this instance.     

Relationship between drinking and increase in tail skin temperature of rats treated with L-5-hydroxytryptophan

Administration of L-5-hydroxytryptophan (25 micrograms/kg, s.c.), the immediate precursor of serotonin, to rats induces drinking and increases tail skin temperature. Decreases in both the metabolic rate (rate of oxygen consumption) and colonic temperature also occur. These responses are similar to those observed following acute administration of angiotensin II. However, both drinking and the increase in tail skin temperature are unaffected by prior administration of the non-peptide angiotensin II, AT-1 receptor antagonist, losartan potassium, but are partially attenuated by the beta-adrenoceptor antagonist, propranolol. This suggests that the responses are independent of the angiotensin AT-1 receptor but may be mediated, in part at least, by the beta-adrenoceptor. The hypothesis is presented that when either L-5-hydroxytryptophan or angiotensin II is administered to rats, they act centrally to reduce the set-point for body temperature regulation, thus resulting in the reflex activation of mechanisms that reduce body temperature, including an increase in tail skin temperature and a decrease in metabolic rate.     

The substitution of proline 35 by alanine in Rhodobacter capsulatus cytochrome c2 affects the overall protein stability but not the alkaline transition

It was shown by Koshy et al. [1990, Proc. Natl Acad. Sci USA, 87, 8697- 8701; 1994, Biochem. J., 299, 347-350] that the substitution of proline 30 by alanine (P30A) of Drosophila melanogaster and rat cytochromes c exhibited decreased stabilities in both the heme iron-methionine sulfur (Fe-S) bond and overall protein conformation. Now we have found that the stability properties of the equivalent mutant of Rhodobacter capsulatus cytochrome c2 (P35A) are somewhat different. Based on optical and NMR spectroscopies, the Rb.capsulatus P35A alkaline transition (pKalk) was found to be unchanged with respect to the wild type, suggesting that the mutation in Rb.capsulatus cytochrome c2 has little effect on the stability of the Fe-S bond. However, Rb.capsulatus conformational stability was found to be decreased by 1.6 kcal/mol in the oxidized state. The difference in the stability properties of the equivalent proline to alanine substitutions in various species underscores the importance of studying mutations in more than one species before drawing generalizations about the role of conserved residues in protein structure and function.      

Occlusion of patent ductus using the Rashkind system. Initial experience]

Three patients were submitted to the Rashkind device technique for closure of a patent ductus arteriosus. The percutaneous transvenous technique was employed in every cases. A 12 mm prosthesis was utilized in one case and 17 mm prostheses in the other two cases. In the first case, after temporary occlusion of the ductus arteriosus, the prostheses was removed due to the technical impossibility of evaluation of the proximal umbrella position. In the second and third cases, the prostheses were duly liberated in the proper position, thus occluding the defects. This technique does not require general anesthesia, is indicated in patients over 6 kgs of body weight, and is a therapeutic alternative to the habitual surgical procedure.     

Use of a magnified cardiac airflow oscillation to classify neonatal apnea

Currently the classification of neonatal apnea relies upon an inference of airway closure based upon the presence of breathing efforts against such an obstruction. In this study we evaluate a new method of classification which utilizes the presence or absence of cardiac airflow oscillation to detect airway closure. Specifically, this evaluation consisted of an examination of the transmission characteristics of an artificially produced airflow oscillation through discrete airway narrowing in a model system; a confirmation that voluntary upper airway occlusion in adult volunteers uniformly induces complete loss of the oscillation; and a comparison of the cardiac oscillation method with the traditional method of apnea classification in a cohort of 4,309 apneas in 32 infants. We determined that the amplitude of the oscillation is negatively correlated with resistance (r = 0.97) and positively with the radius (r = 0.98) of narrowing in a model system, and that voluntary airway obstruction in adult subjects uniformly results in loss of transmitted cardiac oscillations. Moreover, although there was similarity in the frequency distribution of central, obstructive, and mixed apneas in our infants, there were statistically significantly greater obstructive events detected by the cardiac oscillation method. In addition, the cardiac oscillation method had the additional advantage of providing information regarding the timing of airway obstruction during apnea.