Antimicrobial and toxicological evaluation of Origanum vulgare: an in vivo study / Avaliação antimicrobiana e toxicológica de Origanum vulgare: um estudo in vivo

Origanum vulgare has been of great interest in academia and pharma industry due to its antioxidant, antifungal and antitumor properties. The present study aimed to find the anti-MRSA potential and in vivo toxicity assessments of O. vulgare. O. vulgare extract was used to monitor anti-MRSA activity in mice. Following MRSA established infection in mice (Mus musculus), treatment with O. vulgare was continued for 7 days. Autopsies were performed and re-isolation, gross lesion scoring and bacterial load in various organs were measured. Additionally, blood sample was analysed for hematological assays. Toxicity assessment of O. vulgare potential as medicine was done at 200 mg/kg and 400 mg/kg by evaluating liver and kidney functions. Bacterial load and gross lesion in lungs and heart were significantly low compared to positive control following O. vulgare treatment. Likewise, O. vulgare treated groups had hematological, neutrophil and TLC values similar to control groups. Increased AST, ALP and total bilirubin along with marked hepatocellular degeneration and distortion around the central vein, inflammatory cell infiltration, and cytoplasmic vacuolization of hepatic cells was observed at higher dose. It is concluded that crude extract of O. vulgare may contain beneficial secondary metabolites and in future may be explored for curing infectious diseases.

Origanum vulgare tem despertado grande interesse na academia e na indústria farmacêutica devido às suas propriedades antioxidantes, antifúngicas e antitumorais. O presente estudo teve como objetivo encontrar o potencial anti-MRSA e avaliações de toxicidade in vivo de O. vulgare. O extrato de O. vulgare foi usado para monitorar a atividade anti-MRSA em camundongos. Após infecção estabelecida por MRSA em camundongos (Mus musculus), o tratamento com O. vulgare foi continuado por 7 dias. As autópsias foram realizadas e o reisolamento, pontuação das lesões grosseiras e carga bacteriana em vários órgãos foram medidos. Além disso, a amostra de sangue foi analisada para ensaios hematológicos. A avaliação da toxicidade do potencial de O. vulgare como medicamento foi feita com 200 mg / kg e 400 mg / kg, avaliando as funções hepática e renal. A carga bacteriana e as lesões graves nos pulmões e no coração foram significativamente baixas em comparação com o controle positivo após o tratamento com O. vulgare. Da mesma forma, os grupos tratados com O. vulgare apresentaram valores hematológicos, de neutrófilos e de TLC semelhantes aos grupos de controle. Aumento de AST, ALP e bilirrubina total juntamente com degeneração hepatocelular marcada e distorção ao redor da veia central, infiltração de células inflamatórias e vacuolização citoplasmática de células hepáticas foram observados em doses mais altas. Conclui-se que o extrato bruto de O. vulgare pode conter metabólitos secundários benéficos e, no futuro, pode ser explorado para a cura de doenças infecciosas.

Patterning of papillae on the mouse tongue: A system for the quantitative assessment of planar cell polarity signaling.

The dorsal surface of the mouse tongue is covered by ~7000 papillae, asymmetric epithelial protrusions that are precisely oriented to create a stereotyped macroscopic pattern. Within the context of this large-scale pattern, neighboring papillae exhibit a high degree of local order that minimizes the differences in their orientations. We show here that the orientations of lingual papillae are under the control of the core planar cell polarity (PCP) genes Vangl1, Vangl2, and Celsr1. Using K14-Cre and Nkx2.5-Cre to induce conditional knockout of Vangl1 and/or Vangl2 in the tongue epithelium, we observe more severe disruptions to local order among papillae with inactivation of larger numbers of Vangl genes, a greater role for Vangl2 than Vangl1, and a more severe phenotype with the Vangl2 Looptail (Lp) allele than the Vangl2 null allele, consistent with a dominant negative mode of action of the Vangl2Lp allele. Interestingly, Celsr1-/- tongues show disruption of both local and global order, with many papillae in the anterior tongue showing a reversed orientation. To quantify each of these phenotypes, we have developed and applied three procedures for sampling the orientations of papillae and assessing the degree of order on different spatial scales. The experiments reported here establish the dorsal surface of the mouse tongue as a favorable system for studying PCP control of epithelial patterning.

A comparative assessment of mandible shape in a consomic strain panel of the house mouse (Mus musculus)--implications for epistasis and evolvability of quantitative traits.

BACKGROUND: Expectations of repeatedly finding associations between given genes and phenotypes have been borne out by studies of parallel evolution, especially for traits involving absence or presence of characters. However, it has rarely been asked whether the genetic basis of quantitative trait variation is conserved at the intra- or even at the interspecific level. This question is especially relevant for shape, where the high dimensionality of variation seems to require a highly complex genetic architecture involving many genes. RESULTS: We analyse here the genetic effects of chromosome substitution strains carrying M. m. musculus chromosomes in a largely M. m. domesticus background on mandible shape and compare them to the results of previously published QTL mapping data between M. m. domesticus strains. We find that the distribution of genetic effects and effect sizes across the genome is consistent between the studies, while the specific shape changes associated with the chromosomes are different. We find also that the sum of the effects from the different M. m. musculus chromosomes is very different from the shape of the strain from which they were derived, as well as all known wild type shapes. CONCLUSIONS: Our results suggest that the relative chromosome-wide effect sizes are comparable between the long separated subspecies M. m. domesticus and M. m. musculus, hinting at a relative stability of genes involved in this complex trait. However, the absolute effect sizes and the effect directions may be allele-dependent, or are context dependent, i.e. epistatic interactions appear to play an important role in controlling shape.

Stochastic morphometric model of the BALB/c mouse lung.

The laboratory mouse is often used as a human surrogate in aerosol inhalation studies. Morphometric data on the tracheobronchial geometry of three in situ lung casts of the Balb/c mouse lung produced by the Air Pollution Health Effects Laboratory were analyzed in terms of probability density functions and correlations among the different airway parameters. The results of this statistical analysis reveal significant differences in diameters and branching angles between major and minor progeny branching off from the same parent airway at a given airway bifurcation. Number of bronchial airways generations along a given path, expressed by the termination probability, branching angles, and daughter-to-parent diameter ratios indicate that the location of an airway with defined linear airway dimensions within the lung is more appropriately identified by its diameter (or its parent diameter) than by an assigned generation number. We, therefore, recommend classifying the mouse lung airways by their diameters and not by generation numbers, consistent with our previous analysis of the rather monopodial structure of the rat lung (Koblinger et al., J Aerosol Med 1995;8:7­19; Koblinger and Hofmann, J Aerosol Med 1995;8:21­32). Because of lack of corresponding information on respiratory airways, a partly stochastic symmetric acinar airway model was attached to the tracheobronchial model, in which the number of acinar airways along a given path was randomly selected from a measured acinar volume distribution. The computed distributions of the geometric airway parameters and their correlations will be used for random pathway selection of inhaled particles in subsequent Monte Carlo deposition calculations.

Effects of size, sex, and voluntary running speeds on costs of locomotion in lines of laboratory mice selectively bred for high wheel-running activity.

Selective breeding for over 35 generations has led to four replicate (S) lines of laboratory house mice (Mus domesticus) that run voluntarily on wheels about 170% more than four random-bred control (C) lines. We tested whether S lines have evolved higher running performance by increasing running economy (i.e., decreasing energy spent per unit of distance) as a correlated response to selection, using a recently developed method that allows for nearly continuous measurements of oxygen consumption (VO2) and running speed in freely behaving animals. We estimated slope (incremental cost of transport [COT]) and intercept for regressions of power (the dependent variable, VO2/min) on speed for 49 males and 47 females, as well as their maximum VO2 and speeds during wheel running, under conditions mimicking those that these lines face during the selection protocol. For comparison, we also measured COT and maximum aerobic capacity (VO2max) during forced exercise on a motorized treadmill. As in previous studies, the increased wheel running of S lines was mainly attributable to increased average speed, with males also showing a tendency for increased time spent running. On a whole-animal basis, combined analysis of males and females indicated that COT during voluntary wheel running was significantly lower in the S lines (one-tailed P=0.015). However, mice from S lines are significantly smaller and attain higher maximum speeds on the wheels; with either body mass or maximum speed (or both) entered as a covariate, the statistical significance of the difference in COT is lost (one-tailed P> or =0.2). Thus, both body size and behavior are key components of the reduction in COT. Several statistically significant sex differences were observed, including lower COT and higher resting metabolic rate in females. In addition, maximum voluntary running speeds were negatively correlated with COT in females but not in males. Moreover, males (but not females) from the S lines exhibited significantly higher treadmill VO2max as compared to those from C lines. The sex-specific responses to selection may in part be consequences of sex differences in body mass and running style. Our results highlight how differences in size and running speed can account for lower COT in S lines and suggest that lower COT may have coadapted in response to selection for higher running distances in these lines.

Independence between developmental stability and canalization in the skull of the house mouse.

The relationship between the two components of developmental homeostasis, that is canalization and developmental stability (DS), is currently debated. To appraise this relationship, the levels and morphological patterns of interindividual variation and fluctuating asymmetry were assessed using a geometric morphometric approach applied to the skulls of laboratory samples of the house mouse. These three samples correspond to two random-bred strains of the two European subspecies of the house mouse and their F1 hybrids. The inter- and intraindividual variation levels were found to be smaller in the hybrid group compared to the parental ones, suggesting a common heterotic effect on skull canalization and DS. Both buffering mechanisms might then depend on the same genetic condition, i.e. the level of heterozygosity. However, related morphological patterns did not exhibit any congruence. In contradiction with previous studies on insect wing traits, we therefore suggest that canalization and DS may not act on the same morphological characters. The fact that this discrepancy could be related to the functional importance of the symmetry of the characters under consideration is discussed in the light of our knowledge of the genetic bases of both components of developmental homeostasis.

A method of endotracheal intubation and pulmonary functional assessment for repeated studies in mice.

The ability to successfully intubate the trachea of mice and control their ventilation is important for longitudinal studies requiring recovery from anesthesia and repeated pulmonary function measurements or other evaluations, such as the use of radiological imaging (e.g., computed tomography or magnetic resonance imaging). We describe a method for rapid and repeated intubation of mice, with subsequent pulmonary function measurements at baseline and after an agonist challenge. We describe a simply constructed metal blade used as a laryngoscope to facilitate oropharyngeal exposure, transillumination of the neck to facilitate visualization of the trachea through the oropharynx, readily available polyethylene tubing to intubate the trachea, and a simple solenoid ventilator to maintain physiological ventilation and assess respiratory resistance and compliance. Brief infusions of acetylcholine through a needle into the jugular vein are used to assess the responsiveness of the airway smooth muscle.

Mapping quantitative trait loci for body weight on the X chromosome in mice. II. Analysis of congenic backcrosses.

In a QTL mapping study with an F2 population of mice, we have shown that one or more sex-linked factors account for a large part of the divergence between mouse lines selected for high and low body weight. Here, we describe a study undertaken to map the putative X-linked quantitative trait loci (QTLs) by backcrossing segments of chromosome from the high line onto an inbred line derived from the low line, thereby removing possible contributions from the autosomes and linked segments of the X chromosome. Sublines containing a regional at the proximal end of the X chromosome were found to be associated with large differences in body weight, and to account for almost all the difference between the lines. A Markov chain Monte Carlo based multipoint linkage analysis incorporating the available marker and phenotypic information from the backcross pedigree was used to map the QTL to a region of about 6 cM. There was no evidence for QTLs elsewhere on the chromosome. The estimated QTL effect is approximately 20% of mean body weight in males and females at 10 weeks. From results obtained from this study and the accompanying F2 analysis, we conclude the presence of a single factor for body weight localizing to about position (+/- SE) 26.4 +/- 1.2 cM on the X chromosome, which increases body weight by approximately 18% at 10 weeks. A strategy to positionally clone the QTL is discussed.