Medicinal products: regulation of biosynthesis in space and time

We live in a "Demon-Haunted World". Human health care requires the ever increasing resistance of pathogens to be confronted by a correspondingly fast rate of discovery of novel antibiotics. One of the possible strategies towards this objective involves the rational localization of bioactive phytochemicals. The conceptual basis of the method consists in the surprisingly little known gearings of natural products with morphology, ecology and evolution of their plant source, i. e. an introspection into the general mechanisms of nature.

Pulmonary tuberculosis in São Luis, State of Maranhão, Brazil: space and space-time risk clusters for death (2008-2012)

INTRODUCTION: The objective was to identify space and space-time risk clusters for the occurrence of deaths in a priority city for the control of tuberculosis (TB) in the Brazilian Northeast. METHODS: Ecological research was undertaken in the City of São Luis/Maranhão. Cases were considered that resulted in deaths in the population living in the urban region of the city with pulmonary TB as the basic cause, between 2008 and 2012. To detect space and space-time clusters of deaths due to pulmonary TB in the census sectors, the spatial analysis scan technique was used. RESULTS: In total, 221 deaths by TB occurred, 193 of which were due to pulmonary TB. Approximately 95% of the cases (n=183) were geocoded. Two significant spatial clusters were identified, the first of which showed a mortality rate of 5.8 deaths per 100,000 inhabitants per year and a high relative risk of 3.87. The second spatial cluster showed a mortality rate of 0.4 deaths per 100,000 inhabitants per year and a low relative risk of 0.10. A significant cluster was observed in the space-time analysis between 11/01/2008 and 04/30/2011, with a mortality rate of 8.10 deaths per 100,000 inhabitants per year and a high relative risk (3.0). CONCLUSIONS: The knowledge of priority sites for the occurrence of deaths can support public management to reduce inequities in the access to health services and permit an optimization of the resources and teams in the control of pulmonary TB, providing support for specific strategies focused on the most vulnerable populations.

Genetic characterization of rabies virus isolated from bovines and equines between 2007 and 2008, in the States of São Paulo and Minas Gerais

INTRODUCTION: Rabies is an acute disease of the central nervous system and is responsible for the deaths of thousands of humans, wild animals and livestock, particularly cattle, as well as causing major economic losses. This study describes the genetic characterization of rabies virus variants that circulate in Desmodus rotundus populations and are transmitted to herbivores. METHODS: Fifty rabies virus isolates from bovines and equines in the States of São Paulo and Minas Gerais, Brazil, were genetically characterized and compared with sequences retrieved from GenBank. RESULTS: Two clusters (I and II) with mean nucleotide identities of 99.1 and 97.6% were found. The first of these contained nearly all the samples analyzed. Lineages from other Brazilian states grouped in cluster II. CONCLUSIONS: Analysis of the amino acid sequences of the N proteins revealed the existence of genetic markers that may indicate possible variations between geographic regions, although the biologically active regions are conserved within the species over space and time.

Behavior of triatomines (Hemiptera, Reduviidae) vectors of Chagas' disease. II. Influence of feeding, lighting and time of day on the number of mating, mating speed and duration of copulation of Panstrongylus megistus (Burm, 1835) under laboratory conditions

To determine in influence of feeding, lighting and time of day on the copulating behavior of Panstrongylus megistus, 480 insect pairs were divided into four groups of 120 each and tested in the following respective situations: without food deprivation (F.D.), with five days of F.D., with ten days of F.D., and with 20 days of F. D. The tests were performed between 9:00 a.m. to 12:00a.m. and 7:00 p.m. to 10:00 p.m., with light (700-1400 lux) and in the dark (1.4-2.8 lux) and behavior was recorded by the time sampling technique. Mating spped (MS) and duration of copulation (DC) were also calculated for each situation. The maximum frequency of copulation was observed after five days of F.D., at night, in the dark (n = 16), and the minimum was observed for recently-fed pairs, at night, with light (n = 4). Males approached females more often than females approached males. MS was lowest in pairs with twenty days of F.D., at night, with light (X = 23.0 ± 16.0 minutes), and highest in recently-fed pairs, during the day, with light (X = 2.9 ± 2.5 minutes). DC was shortest in recently-fed insects, during the day, in the dark (X = 23.5 ± 6.7 minutes), and longest in recently-fed animals, at night, in the dark (X = 38.3 ± 6.9 minutes).

Preferential transcription of Paracoccidioides brasiliensis genes: host niche and time-dependent expression

Paracoccidioides brasiliensis causes infection through inhalation by the host of airborne propagules from the mycelium phase of the fungus. This fungus reaches the lungs, differentiates into the yeast form and is then disseminated to virtually all parts of the body. Here we review the identification of differentially-expressed genes in host-interaction conditions. These genes were identified by analyzing expressed sequence tags (ESTs) from P. brasiliensis cDNA libraries. The P. brasiliensis was recovered from infected mouse liver as well as from fungal yeast cells incubated in human blood and plasma, mimicking fungal dissemination to organs and tissues and sites of infection with inflammation, respectively. In addition, ESTs from a cDNA library of P. brasiliensis mycelium undergoing the transition to yeast were previously analyzed. Together, these studies reveal significant changes in the expression of a number of genes of potential importance in the host-fungus interaction. In addition, the unique and divergent representation of transcripts when the cDNA libraries are compared suggests differential gene expression in response to specific niches in the host. This analysis of gene expression patterns provides details about host-pathogen interactions and peculiarities of sites within the host.

Spatial and temporal dynamics of drosophilid larval assemblages associated to fruits

The study of organisms and their resources is critical to further understanding population dynamics in space and time. Although drosophilids have been widely used as biological models, their relationship with breeding and feeding sites has received little attention. Here, we investigate drosophilids breeding in fruits in the Brazilian Savanna, in two contrasting vegetation types, throughout 16 months. Specifically, larval assemblages were compared between savannas and forests, as well as between rainy and dry seasons. The relationships between resource availability and drosophilid abundance and richness were also tested. The community (4,022 drosophilids of 23 species and 2,496 fruits of 57 plant taxa) varied widely in space and time. Drosophilid assemblages experienced a strong bottleneck during the dry season, decreasing to only 0.5% of the abundance of the rainy season. Additionally, savannas displayed lower richness and higher abundance than the forests, and were dominated by exotic species. Both differences in larval assemblages throughout the year and between savannas and gallery forests are consistent with those previously seen in adults. Although the causes of this dynamic are clearly multifactorial, resource availability (richness and abundance of rotten fruits) was a good predictor of the fly assemblage structure.

Political philosophy, ethnology, and time: a study of the notion of historical handicap

This article starts by identifying the crucial importance of the notion of historical handicap for the present-day social sciences of Latin America. Such notion is not an original invention made by Latinamericanists. On the contrary, I demonstrate that the genealogy of the notion of historical handicap must be sought in the tradition of Western political philosophy. Such genealogy must take into account the way it was integrated into ethnological descriptions. When and how did the Other become the backward, the primitive? While this relation was secondary for ancient Greek thought, theories of historical development became the main source of ethnological categories in the modern era. Interestingly enough, this modern synthesis suited the practical purpose of justifying two successive waves of European imperialistic: the era of discoveries, and 19th century colonialism. The article concludes by raising questions about the present role and application of the social sciences.

Character transformations and their functional significance as a key to the evolution of hystricognath Rodentia

Hystricognathi represent a monophyletic taxon within Rodentia. Since phylogenetically analyzed morphological systems are essential for revealing evolutionary processes, this study identifies evolutionary character transformations on the stem lineage of Hystricognathi as derived from the author's own work and the literature. Data so far indicate that evolutionary transformations in the rostral head region, the loss of tactile ability in the outer nasal skin and the mobile arrangement of the associated cartilage, were allied with a switch from omnivorous to herbivorous and fiber-rich nutrition. Additional character transformations in the skull assist in digesting such food. Structures associated with reproduction and placentation show a remarkable pro portion of derived character conditions: the chorioallantoic placenta has a ring-shaped organization and growth structure which optimizes the capacity for passive diffusion, a subplacenta occurred as a specialized region responsible for placental invasion and the inverted yolk sac facilitates substance exchange with the main placenta. Finally, precocial newborns evolved as a derived condition within Rodentia. All things considered, a mode of reproduction is indicated, which does not demand excessive additional energy intake by the mother and is in accordance with her low energetic diet. Hystricognathi possess major character transformations that represent prerequisites for their successful radiation at the time when more open ecosystems and grasslands evolved during Earth history. The analysis resulted in the reconstruction of a life-near picture of the hystricognath stem species pattern with high explanatory power in terms of changes in space and time and their interdependence with biodiversity.

Floristic and structural variation of weeds in eucalyptus plantations as influenced by relief and time of year

The objective of this work was to analyze the floristic variation and phytosociological structure of weeds as influenced by relief and time of year in eucalyptus plantations in Santana do Paraíso and Guanhães - MG. The total area sampled for each locality was approximately 10 ± 3 hectares, comprising three types of relief: lowland, slope, and upper area. In each type of relief, 10 plots of 1 m² were sampled, corresponding to 30 plots per locality, where they were randomly allocated in a zigzag. The taxonomic identification was performed in four assessments, corresponding to the months of November and March, comprising two ratings each season, always at the same points, and geo-referenced using the Global Positioning System (GPS). A total of 3,893 individuals, 18 families and 61 species, were identified in Santana do Paraiso and a total of 1,166 individuals, 13 families and 58 species, in Guanhães. In both localities, the most representative families in terms of wealth were: Poaceae, Asteraceae, and Fabaceae. Galinsoga parviflora was the most abundant species. The Vernonia polyantes was identified only in the lowlands, while Arrabida florida was identified in the slope and upper area. On the other hand, Emilia coccinea, Sida rhombifolia, S. paniculatum and Spermacoce latifolia were common to all three environments. Commelina benghalensis was present only in the month of March, while G. parviflora was present only in the month of November. It was concluded that the floristic and phytosociological variation of weeds in eucalyptus plantations is influenced by the type of relief and time of year, which should guide the management practices used in the culture.

Inulin production by Vernonia herbacea as influenced by mineral fertilization and time of harvest

The underground organs of Vernonia herbacea (Vell.) Rusby, known as rhizophores, acumulate 80% of their dry mass as fructans of the inulin type. In view of the growing industrial use of fructans as dietetic and general food products, and of their medical application, the present investigation aimed at evaluating the effect of mineral fertilization and period of cultivation on the production of these carbohydrates in field trials. Plants used in the experiments were obtained by vegetative propagation from rhizophores collected from plants growing in natural areas of the cerrado, and cultivated for two years. Fertilization consisted of N:P2O5:K2O (80:200:150 kg.ha-1) plus 80 kg.ha-1 nitrogen as dressing. Soil fertilization did not stimulate biomass or inulin production, but in the second year of cultivation a dramatic gain in biomass and inulin was detected in both treated and control plants. Inulin production varied from 113 to 674 kg.ha-1 which corresponds to 43% of the rhizophore dry mass. The composition of fructans was not altered by fertilization, although treated plants had a higher proportion of sucrose and fructans with degree of polymerization 3-8 in the second year of cultivation. The results identify this species as a fructan source similar to other commercial crops and recommend further agronomic studies, aimed at increasing the production of this polysaccharide.

Pressure and time dependence of the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy

The first minutes of the time course of cardiopulmonary reflex control evoked by lower body negative pressure (LBNP) in patients with hypertensive cardiomyopathy have not been investigated in detail. We studied 15 hypertensive patients with left ventricular dysfunction (LVD) and 15 matched normal controls to observe the time course response of the forearm vascular resistance (FVR) during 3 min of LBNP at -10, -15, and -40 mmHg in unloading the cardiopulmonary receptors. Analysis of the average of 3-min intervals of FVR showed a blunted response of the LVD patients at -10 mmHg (P = 0.03), but a similar response in both groups at -15 and -40 mmHg. However, using a minute-to-minute analysis of the FVR at -15 and -40 mmHg, we observed a similar response in both groups at the 1st min, but a marked decrease of FVR in the LVD group at the 3rd min of LBNP at -15 mmHg (P = 0.017), and -40 mmHg (P = 0.004). Plasma norepinephrine levels were analyzed as another neurohumoral measurement of cardiopulmonary receptor response to LBNP, and showed a blunted response in the LVD group at -10 (P = 0.013), -15 (P = 0.032) and -40 mmHg (P = 0.004). We concluded that the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy is blunted at lower levels of LBNP. However, at higher levels, the cardiopulmonary reflex has a normal initial response that decreases progressively with time. As a consequence of the time-dependent response, the cardiopulmonary reflex response should be measured over small intervals of time in clinical studies.

Plasma amino acids in pregnancy, placental intervillous space and preterm newborn infants

Plasma amino acid levels have never been studied in the placental intervillous space of preterm gestations. Our objective was to determine the possible relationship between plasma amino acids of maternal venous blood (M), of the placental intervillous space (PIVS) and of the umbilical vein (UV) of preterm newborn infants. Plasma amino acid levels were analyzed by ion-exchange chromatography in M from 14 parturients and in the PIVS and UV of their preterm newborn infants. Mean gestational age was 34 ± 2 weeks, weight = 1827 ± 510 g, and all newborns were considered adequate for gestational age. The mean Apgar score was 8 and 9 at the first and fifth minutes. Plasma amino acid values were significantly lower in M than in PIVS (166%), except for aminobutyric acid. On average, plasma amino acid levels were significantly higher in UV than in M (107%) and were closer to PIVS than to M values, except for cystine and aminobutyric acid (P < 0.05). Comparison of the mean plasma amino acid concentrations in the UV of preterm to those of term newborn infants previously studied by our group showed no significant difference, except for proline (P < 0.05), preterm > term. These data suggest that the mechanisms of active amino acid transport are centralized in the syncytiotrophoblast, with their passage to the fetus being an active bidirectional process with asymmetric efflux. PIVS could be a reserve amino acid space for the protection of the fetal compartment from inadequate maternal amino acid variations.

Relationship between Brazilian airline pilot errors and time of day

Flight safety is one of the most important and frequently discussed issues in aviation. Recent accident inquiries have raised questions as to how the work of flight crews is organized and the extent to which these conditions may have been contributing factors to accidents. Fatigue is based on physiologic limitations, which are reflected in performance deficits. The purpose of the present study was to provide an analysis of the periods of the day in which pilots working for a commercial airline presented major errors. Errors made by 515 captains and 472 copilots were analyzed using data from flight operation quality assurance systems. To analyze the times of day (shifts) during which incidents occurred, we divided the light-dark cycle (24:00) in four periods: morning, afternoon, night, and early morning. The differences of risk during the day were reported as the ratio of morning to afternoon, morning to night and morning to early morning error rates. For the purposes of this research, level 3 events alone were taken into account, since these were the most serious in which company operational limits were exceeded or when established procedures were not followed. According to airline flight schedules, 35% of flights take place in the morning period, 32% in the afternoon, 26% at night, and 7% in the early morning. Data showed that the risk of errors increased by almost 50% in the early morning relative to the morning period (ratio of 1:1.46). For the period of the afternoon, the ratio was 1:1.04 and for the night a ratio of 1:1.05 was found. These results showed that the period of the early morning represented a greater risk of attention problems and fatigue.

Effect of melatonin and time of administration on irradiation-induced damage to rat testes

The effect of ionizing irradiation on testes and the protective effects of melatonin were investigated by immunohistochemical and electron microscopic methods. Eighty-two adult male Wistar rats were divided into 10 groups. The rats in the irradiated groups were exposed to a sublethal irradiation dose of 8 Gy, either to the total body or abdominopelvic region using a 60Co source at a focus of 80 cm away from the skin in the morning or evening together with vehicle (20% ethanol) or melatonin administered 24 h before (10 mg/kg), immediately before (20 mg/kg) and 24 h after irradiation (10 mg/kg), all ip. Caspace-3 immunoreactivity was increased in the irradiated group compared to control (P < 0.05). Melatonin-treated groups showed less apoptosis as indicated by a considerable decrease in caspace-3 immunoreactivity (P < 0.05). Electron microscopic examination showed that all spermatogenic cells, especially primary spermatocytes, displayed prominent degeneration in the groups submitted to total body and abdominopelvic irradiation. However, melatonin administration considerably inhibited these degenerative changes, especially in rats who received abdominopelvic irradiation. Total body and abdominopelvic irradiation induced identical apoptosis and testicular damage. Chronobiological assessment revealed that biologic rhythm does not alter the inductive effect of irradiation. These data indicate that melatonin protects against total body and abdominopelvic irradiation. Melatonin was more effective in the evening abdominopelvic irradiation and melatonin-treated group than in the total body irradiation and melatonin-treated group.

Correlations of circulating peptide YY and ghrelin with body weight, rate of weight gain, and time required to achieve the recommended daily intake in preterm infants

The objective was to elucidate the relationships between serum concentrations of the gut hormone peptide YY (PYY) and ghrelin and growth development in infants for potential application to the clinical observation index. Serum concentrations of PYY and ghrelin were measured using radioimmunoassay from samples collected at the clinic. For each patient, gestational age, birth weight, time required to return to birth weight, rate of weight gain, time required to achieve recommended daily intake (RDI) standards, time required for full-gastric feeding, duration of hospitalization, and time of administration of total parenteral nutrition were recorded. Serum PYY and ghrelin concentrations were significantly higher in the preterm group (N = 20) than in the full-term group (N = 20; P < 0.01). Within the preterm infant group, the serum concentrations of PYY and ghrelin on postnatal day (PND) 7 (ghrelin = 1485.38 ± 409.24; PYY = 812.37 ± 153.77 ng/L) were significantly higher than on PND 1 (ghrelin = 956.85 ± 223.09; PYY = 545.27 ± 204.51 ng/L) or PND 3 (ghrelin = 1108.44 ± 351.36; PYY = 628.96 ± 235.63 ng/L; P < 0.01). Both serum PYY and ghrelin concentrations were negatively correlated with body weight, and the degree of correlation varied with age. Serum ghrelin concentration correlated negatively with birth weight and positively with the time required to achieve RDI (P < 0.05). In conclusion, serum PYY and ghrelin concentrations reflect a negative energy balance, predict postnatal growth, and enable compensation. Further studies are required to elucidate the precise concentration and roles of PYY and ghrelin in newborns and to determine the usefulness of measuring these hormones in clinical practice.