Childhood asthma on the northern Mexico border

Children with asthma living on the northern Mexico border suffer not only from the physical aspects of this condition, but also from the lack of a clear biomedical definition and treatment plan for the illness. An ethnographic study involving participant observation and focused interviews in Tijuana, Mexico, sought to understand the intersection of diagnostic uncertainties surrounding childhood asthma on the part of parents, particularly mothers, living in acute poverty. Environmental factors such as dust and insects in impoverished homes probably acted as asthma triggers among many of the children in the study. Furthermore, management of children's asthma took place not only in biomedical clinics, but also in homes, traditional medical settings, and pharmacies, where mothers often sought remedies for their children's asthma attacks on an emergency basis. In all treatment settings, including biomedical ones, they often faced significant barriers to effective care, including the misuse of antibiotics. Thus, the role of pharmaceutical sales clerks, as well as pediatric asthma specialists, is explored in this article.     

Depressed thermogenesis but competent brown adipose tissue recruitment in mice devoid of all hormone-binding thyroid hormone receptors

We have examined the metabolic role of hormone-binding nuclear thyroid hormone receptors (TRs). Mice devoid of all hormone-binding TRs [TR alpha 1(-/-)beta(-/-) (TR-ablated mice)] had slightly decreased body temperature and much decreased basal metabolic rate, were still able to markedly increase metabolic rate in the cold, but were cold intolerant due to inadequate total heat production at low temperatures. A standard norepinephrine test showed that adrenergically induced thermogenesis could not be activated normally in the TR-ablated mice. This was not due to inadequate recruitment of brown adipose tissue, nor to the absence, decreased recruitment or dysfunction of the uncoupling protein-1. However, isolated brown fat cells were 10-fold desensitized, explaining the lack of response to standard adrenergic stimuli; cell culture experiments demonstrated that this desensitization was not an innate effect. Thus, the cold intolerance was probably not due to inadequate sympathetically induced nonshivering thermogenesis. Additionally, the results indicated that no metabolic effects of thyroid hormones could become manifest in the absence of nuclear TRs, that ligand-bound TRs were needed for euthermia and eumetabolism, but that TRs per se were not required for brown adipose tissue recruitment and uncoupling protein-1 gene expression.     

Left ventricular pressure-volume relationship in a rat model of advanced aging-associated heart failure

Aging is associated with profound changes in the structure and function of the heart. A fundamental understanding of these processes, using relevant animal models, is required for effective prevention and treatment of cardiovascular disease in the elderly. Here, we studied cardiac performance in 4- to 5-mo-old (young) and 24- to 26-mo-old (old) Fischer 344 male rats using the Millar pressure-volume (P-V) conductance catheter system. We evaluated systolic and diastolic function in vivo at different preloads, including preload recruitable stroke work (PRSW), maximal slope of the systolic pressure increment (+dP/dt), and its relation to end-diastolic volume (+dP/dt-EDV) as well as the time constant of left ventricular pressure decay, as an index of relaxation. The slope of the end-diastolic P-V relation (EDPVR), an index of left ventricular stiffness, was also calculated. Aging was associated with decrease in left ventricular systolic pressure, +dP/dt, maximal slope of the diastolic pressure decrement, +dP/dt-EDV, PRSW, ejection fraction, stroke volume, cardiac and stroke work indexes, and efficiency. In contrast, total peripheral resistance, left ventricular end-diastolic volume, left ventricular end-diastolic pressure, and EDPVR were greater in aging than in young animals. Taken together, these data suggest that advanced aging is characterized by decreased systolic performance accompanied by delayed relaxation and increased diastolic stiffness of the heart in male Fischer 344 rats. P-V analysis is a sensitive method to determine cardiac function in rats.     

Spatial variation in frequency and intensity of antibiotic interactions among Streptomycetes from prairie soil

Antibiotic interactions are believed to be significant to microbial fitness in soil, yet little is known of the frequency, intensity, and diversity of antibiotic inhibition and resistance among indigenous microbes. To begin to address these issues, we studied the abilities of streptomycete isolates from prairie soil to inhibit growth and display resistance to antibiotics produced by a test collection of 10 streptomycete isolates. Wide variations in antibiotic inhibition and resistance for prairie isolates among three locations and four soil depths within a 1-m2 plot were revealed. Fewer than 10% of 153 prairie isolates inhibited all 10 test isolates, while more than 40% of the isolates did not inhibit any of the test isolates. No field isolate was resistant to all of the test isolates, nor was any isolate susceptible to all of the test isolates. No correlation between inhibition and resistance phenotypes was found, suggesting that inhibition and resistance are under independent selection. The significant spatial variation in the frequency and intensity of antibiotic inhibition implies that the fitness benefits of antibiotic production are not the same among locations in soil. In contrast, the consistency of resistance over space indicates that its significance to fitness across locations is stable or the costs of maintaining resistance in the absence of selection are small or nonexistent. The spatial clustering of antibiotic inhibitory activity suggests a variable matrix of selection pressures and microbial responses across the soil landscape.     

Comparison of suitability of RAPD and ISSR techniques for determination of strawberry (<Emphasis Type="Italic">Fragaria ×</Emphasis><Emphasis Type="Italic">ananassa</Emphasis> Duch.) relationship

Two PCR-based techniques, RAPD and ISSR, were utilized for determination of genetic relationship of 24 strawberry cultivars used in breeding program at the Research Institute of Pomology and Floriculture in Poland. Polymorphism of investigated genotypes was observed in reactions with 23 out of 48 tested RAPD primes and 41 from 90 tested ISSR primers. Relationship, determined on the base of polymorphic products analysis and showed in the form of dendrograms (UPGMA percent method), was generally similar for both techniques, although similarity values based on ISSR data were higher than those based on RAPD. The parallel use of two data sets seems to allow for precise estimation of cultivars relationship and diminishing mistakes connected with methods' technical limitations.     

Structural and functional characterization of N-terminally blocked peptides isolated from the venom of the social wasp Polybia paulista

Two novel peptides were isolated from the crude venom of the social wasp Polybia paulista, by using RP-HPLC under a gradient of MeCN from 5 to 60% (v/v) and named Polybine-I and -II. Further purification of these peptides under normal phase chromatography, rendered pure enough preparations to be sequenced by Edman degradation chemistry. However, both peptides did not interact with phenylisothiocyanate reagent, suggesting the existence of a chemically blocked N-terminus. Therefore, the sequences of both peptides were assigned by ESI-MS/MS under CID conditions, as follows: Polybine-I Ac-SADLVKKIWDNPAL-NH₂ (Mr 1610 Da) and Polybine-II Ac-SVDMVMKGLKIWPL-NH₂ (Mr 1657 Da). During the tandem mass spectrometry experiments, a loss of 43 a.m.u. was observed from the N-terminal residue of each peptide, suggesting the acetylation of the N-terminus. Subsequently, the peptides with and without acetylation were synthesized on solid phase and submitted to functional characterizations; the biological activities investigated were: hemolysis, chemotaxis of polymorphonucleated leukocytes (PMNL), mast cell degranulation and antibiosis. The results revealed that the acetylated peptides exhibited more pronounced chemotaxis of PMNL cells and mast cell degranulation than the respective non-acetylated congeners; no hemolytic and antibiotic activities were observed, irrespective to the blockage or not of the -amino groups of the N-terminal residues of each peptide. Therefore, the N-terminal acetylation may be related to the increase of the inflammatory activity of both peptides.     

Spiroquinazolinones as novel, potent, and selective PDE7 inhibitors. Part 1

The synthesis and SAR studies of spiroquinazolinones as novel PDE7 inhibitors are discussed. The best compounds from the series displayed nanomolar inhibitory affinity and were selective versus other PDE isoenzymes.     

HIV treatment models with time delay

The present paper shows possible effects of antiretroviral treatment on the dynamics of the spread of the disease of human immunodeficiency virus infection in a population of varying size. By introducing time delays, we model the latency period and the delayed onset of positive treatment effects in the patients. The Hopf bifurcation and stability behaviour of the delay differential-equation model are analysed and simulations for different scenarios depending on the size of the treatment-induced delay are presented, and the results are discussed in detail.