Evaluation of the plasmatic level of mepivacaine in different anatomical regions.

BACKGROUND: To evaluate the serum level of the local anesthetic mepivacaine 3% without vasoconstrictor in patients who underwent procedures performed in the anterior and posterior maxilla, through a method of possible extraction to quantify it in human plasma by high performance liquid chromatography (HPLC). MATERIAL AND METHODS: This was a hybrid study consisting of 18 patients (7 females and 11 males) classified as ASA I, adults and with normal body mass index, submitted to procedures in the anterior region (group I) and posterior region of the maxilla (group II). For 40 minutes, five 6 ml blood samples were collected every 10 minutes after infiltrative injection in each region of the maxilla. Serum levels of the drug were obtained through HPLC. Blood pressure (BP) and heart rate (HR) were measured throughout the procedure. RESULTS: When compared to the general average of the concentrations of each group, significant values (p <0.05) with greater absorption were observed for the anterior region of the maxilla (group I). There was no significant difference when comparing blood pressure (BP) and heart rate (HR) values. CONCLUSIONS: The concentrations found are safe for infiltrative anesthesia in the analyzed patients, there was a higher plasma level of the local anesthetic in the anterior region of the maxilla and there was no change in HR and BP in relation to the anesthetized area.

Approaches to Investigating Complex Genetic Traits in a Large-Scale Inbred Mouse Aging Study.

Inbred mice are a unique model system for studying aging because of the genetic homogeneity within inbred strains, the short life span of mice relative to humans, and the rich array of analytic tools that are available. A large-scale aging study was conducted on 28 inbred strains representing great genetic diversity to determine, via histopathology, the type and diversity of spontaneous diseases that aging mice develop. A total of 20 885 different diagnoses were made, with an average of 12 diagnoses per mouse in the study. Eighteen inbred strains have had their genomes sequenced, and many others have been partially sequenced to provide large repositories of data on genetic variation among the strains. This vast amount of genomic information can be utilized in genome-wide association studies to find candidate genes that are involved in the pathogenesis of spontaneous diseases. As an illustration, this article presents a genome-wide association study of the genetic associations of age-related intestinal amyloidosis, which implicated 3 candidate genes: translocating chain-associated membrane protein 1 (Tram1); splicing factor 3b, subunit 5 (Sf3b5); and syntaxin 11 (Stx11). Representative photomicrographs are available on the Mouse Tumor Biology Database and Pathbase to serve as a reference when evaluating inbred mice used in other genetic or experimental studies to rule out strain background lesions. Many of the age-related mouse diseases are similar, if not identical, to human diseases; therefore, the genetic discoveries have direct translational benefit.

The influence of microhabitat on the population dynamics of four herbaceous species in a semiarid area of northeastern Brazil.

Variation in annual rainfall is considered the most important factor influencing population dynamics in dry environments. However, different factors may control population dynamics in different microhabitats. This study recognizes that microhabitat variation may attenuate the influence of climatic seasonality on the population dynamics of herbaceous species in dry forest (Caatinga) areas of Brazil. We evaluated the influence of three microhabitats (flat, rocky and riparian) on the population dynamics of four herbaceous species (Delilia biflora, Commelina obliqua, Phaseolus peduncularis and Euphorbia heterophylla) in a Caatinga (dry forest) fragment at the Experimental Station of the Agronomic Research Institute of Pernambuco in Brazil, over a period of three years. D. biflora, C. obliqua and P. peduncularis were found in all microhabitats, but they were present at low densities in the riparian microhabitat. There was no record of E. heterophylla in the riparian microhabitat. Population size, mortality rates and natality rates varied over time in each microhabitat. This study indicates that different establishment conditions influenced the population size and occurrence of the four species, and it confirms that microhabitat can attenuate the effect of drought stress on mortality during the dry season, but the strength of this attenuator role may vary with time and species.

The influence of microhabitat on the population dynamics of four herbaceous species in a semiarid area of northeastern Brazil / A influência dos microhabitats sobre a dinâmica de populações de quatro espécies herbáceas em uma área semiárida no nordeste do Brasil

Abstract Variation in annual rainfall is considered the most important factor influencing population dynamics in dry environments. However, different factors may control population dynamics in different microhabitats. This study recognizes that microhabitat variation may attenuate the influence of climatic seasonality on the population dynamics of herbaceous species in dry forest (Caatinga) areas of Brazil. We evaluated the influence of three microhabitats (flat, rocky and riparian) on the population dynamics of four herbaceous species (Delilia biflora, Commelina obliqua, Phaseolus peduncularis and Euphorbia heterophylla) in a Caatinga (dry forest) fragment at the Experimental Station of the Agronomic Research Institute of Pernambuco in Brazil, over a period of three years. D. biflora, C. obliqua and P. peduncularis were found in all microhabitats, but they were present at low densities in the riparian microhabitat. There was no record of E. heterophylla in the riparian microhabitat. Population size, mortality rates and natality rates varied over time in each microhabitat. This study indicates that different establishment conditions influenced the population size and occurrence of the four species, and it confirms that microhabitat can attenuate the effect of drought stress on mortality during the dry season, but the strength of this attenuator role may vary with time and species.

Resumo A variação anual na precipitação é considerada o fator mais importante que influencia a dinâmica populacional em ambientes secos. No entanto, diferentes fatores podem controlar a dinâmica populacional em diferentes microhabitats. A hipótese deste estudo é que as variações de microhabitats podem atenuar a influência da sazonalidade climática sobre a dinâmica populacional de espécies herbáceas em uma áreas floresta seca (Caatinga) no Brasil. Então, objetivou-se avaliar a influência de três microhabitats (plano, rochoso e ciliar) sobre a dinâmica das populações de quatro espécies herbáceas (Delilia biflora, Commelina obliqua, Phaseolus peduncularis e Euphorbia heterophylla) em um fragmento de Caatinga da Estação Experimental do Instituto de Pesquisas Agronômicas de Pernambuco, no Brasil, durante um período de três anos. D. biflora, C. obliqua e P. peduncularis foram encontrados em todos os microhabitats, mas elas estavam presentes em baixas densidades no microhabitat ciliar. Não houve registro de E. heterophylla no microhabitat ciliar. O tamanho das populações, as taxas de mortalidade e de natalidade variaram ao longo do tempo em cada microhabitat. Este estudo indica que diferentes as condições de estabelecimento influenciaram o tamanho das populações e a ocorrência das quatro espécies e confirma que microhabitat pode atenuar o efeito do estresse hídrico sobre a mortalidade durante a estação seca, mas a força desse papel atenuador pode variar com o tempo e a espécie considerada.

The antinociceptive effects of the tetracyclic triterpene euphol in inflammatory and neuropathic pain models: The potential role of PKCε.

Evidences suggest protein kinase C epsilon (PKCε) activation is involved in both inflammatory and neuropathic pains. We have previously shown that tetracyclic triterpene euphol produces antinociception in different models of persistent pain, an action associated with its anti-inflammatory properties. Among these properties are the cannabinoid system activation and different PKC isozymes modulation. Herein, we sought to explore the potential role of PKCε modulation on euphol antinociceptive effect, in inflammatory and neuropathic pain models, in rodents. Also, we investigated further mechanisms associated with euphol effects. Oral treatment with euphol (30 mg/kg) prevented the putative effect of PGE2-induced acute and persistent mechanical hypersensitivity in mice and rats, respectively. In the PGE2-induced acute mechanical hypersensitivity euphol promoted an inhibitory effect similar to a PKCε inhibitor peptide. Likewise, in rats it prevented the mechanical hypersensitivity induced by a PKCε activator. Conversely, euphol effectiveness was not observed in a cAMP/PKA-induced mechanical hypersensitivity in mice. Single (1h prior) or repeated (twice daily during 3 or 13 days) treatments with euphol ameliorated painful peripheral neuropathy induced by paclitaxel and also the mechanical hypersensitivity induced by B16F10 melanoma cells injection, in mice. Additionally, in both inflammatory and neuropathic pain models, euphol consistently prevented PKCε up-regulation, as well as, inhibited the up-regulation of PKCε-activated intracellular pathways; namely nuclear factor-κB (NF-κB), cyclic AMP response element binding protein (CREB) and cyclo-oxygenase-2 (COX-2). The present results suggest the antinociceptive effect on persistent pain caused by euphol is likely dependent on the inhibition of pro-inflammatory mediators modulated by PKCε.

Phenotypic characterization of the KK/HlJ inbred mouse strain.

Detailed histopathological diagnoses of inbred mouse strains are important for interpreting research results and defining novel models of human diseases. The aim of this study was to histologically detect lesions affecting the KK/HlJ inbred strain. Mice were examined at 6, 12, and 20 months of age and near natural death (ie, moribund mice). Histopathological lesions were quantified by percentage of affected mice per age group and sex. Predominant lesions were mineralization, hyperplasia, and fibro-osseous lesions. Mineralization was most frequently found in the connective tissue dermal sheath of vibrissae, the heart, and the lung. Mineralization was also found in many other organs but to a lesser degree. Hyperplasia was found most commonly in the pancreatic islets, and fibro-osseous lesions were observed in several bones. The percentage of lesions increased with age until 20 months. This study shows that KK/HlJ mice demonstrate systemic aberrant mineralization, with greatest frequency in aged mice. The detailed information about histopathological lesions in the inbred strain KK/HlJ can help investigators to choose the right model and correctly interpret the experimental results.

Spatial variation in the structure and composition of the herbaceous community in a semiarid region of northeastern Brazil.

In the arid and semiarid environments of the world, microhabitats serve as models for the structure of vegetation communities. The goal of this study was to identify differences in the structures of the herbaceous communities growing on a crystalline substrate and those growing on a sedimentary substrate in a semiarid region of northeastern Brazil. One hundred 1 × 1 m plots were established in each area for quantitative sampling, with 69 species recorded in the crystalline area and 76 in the sedimentary area. The average plant density was higher in the sedimentary area, and average diameters and heights were greater in the crystalline area. The families and species with a high Importance Value Index (IVI) and a high Mixed Ecological Value Index (MEVI) differed between the areas. Of the species with high densities, only four were found in both areas. Shannon-Weiner diversity index values in the crystalline (2.96 nats/ind.(-1)) and sedimentary (2.89 nats/ind.(-1)) areas were similar. Evenness values on both substrates were also similar (0.72 and 0.71 in the crystalline and sedimentary areas, respectively). This study shows that variations in plant establishment conditions between crystalline and sedimentary areas in a semiarid region of northeastern Brazil should be considered as structure-modeling factors for the herbaceous community.

Natural regeneration of the herbaceous community in a semiarid region in Northeastern Brazil.

This study aimed to describe and compare the interannual changes in the diversity and population structure of herbaceous plants in an anthropogenic area that has been regenerating for 15 years and to identify the similarities and differences in the biological attributes of the community compared with the characteristics of a regenerating conserved area. In total, 105 plots measuring 1 m(2) were established. In each plot, the herbaceous plants were identified, and their height and stem diameter were measured for two consecutive years. The herbaceous flora of the anthropogenic area was represented by 86 species in 70 genera and 27 families, and there were no significant differences in the average richness between years. The conserved area was represented by 71 species in 63 genera and 35 families, and there was a significant difference in the total richness between areas and between years, except when comparing the richness between the conserved area and the anthropogenic area during the second year. Considering both the anthropogenic and conserved areas, 123 herbaceous species were listed, and the similarity between areas was 60 %. For the anthropogenic area, the floristic similarity between years was 95 %, and in the fragment of the conserved area, the similarity was 74 %. The diversity and density were significantly different between years and between areas. Given these results, this study suggests that 15 years of natural regeneration for the caatinga is not sufficient to reestablish its native flora with respect to its herbaceous component.

Development, structure, and keratin expression in C57BL/6J mouse eccrine glands.

Eccrine sweat glands in the mouse are found only on the footpads and, when mature, resemble human eccrine glands. Eccrine gland anlagen were first apparent at 16.5 days postconception (DPC) in mouse embryos as small accumulations of cells in the mesenchymal tissue beneath the developing epidermis resembling hair follicle placodes. These cells extended into the dermis where significant cell organization, duct development, and evidence of the acrosyringium were observed in 6- to 7-postpartum day (PPD) mice. Mouse-specific keratin 1 (K1) and 10 (K10) expression was confined to the strata spinosum and granulosum. In 16.5 and 18.5 DPC embryos, K14 and K17 were both expressed in the stratum basale and diffusely in the gland anlagen. K5 expression closely mimicked K17 throughout gland development. K6 expression was not observed in the developing glands of the embryo but was apparent in the luminal cell layer of the duct by 6 to 7 PPD. By 21 PPD, the gland apertures appeared as depressions in the surface surrounded by cornified squames, and the footpad surface lacked the organized ridge and crease system seen in human fingers. These data serve as a valuable reference for investigators who use genetically engineered mice for skin research.

Primary follicular dystrophy with scarring dermatitis in C57BL/6 mouse substrains resembles central centrifugal cicatricial alopecia in humans.

A number of C57BL/6 (B6) substrains are commonly used by scientists for basic biomedical research. One of several B6 strain-specific background diseases is focal alopecia that may resolve or progress to severe, ulcerative dermatitis. Clinical and progressive histologic changes of skin disease commonly observed in C57BL/6J and preliminary studies in other closely related substrains are presented. Lesions develop due to a primary follicular dystrophy with rupture of severely affected follicles leading to formation of secondary foreign body granulomas (trichogranulomas) in affected B6 substrains of mice. Histologically, these changes resemble the human disease called central centrifugal cicatrical alopecia (CCCA). Four B6 substrains tested have a polymorphism in alcohol dehydrogenase 4 (Adh4) that reduces its activity and potentially affects removal of excess retinol. Using immunohistochemistry, differential expression of epithelial retinol dehydrogenase (DHRS9) was detected, which may partially explain anecdotal reports of frequency differences between B6 substrains. The combination of these 2 defects has the potential to make high dietary vitamin A levels toxic in some B6 substrains while not affecting most other commonly used inbred strains.

Exercise training and detraining modify the morphological and mechanical properties of single cardiac myocytes obtained from spontaneously hypertensive rats.

We determined the effects of exercise training and detraining on the morphological and mechanical properties of left ventricular myocytes in 4-month-old spontaneously hypertensive rats (SHR) randomly divided into the following groups: sedentary for 8 weeks (SED-8), sedentary for 12 weeks (SED-12), treadmill-running trained for 8 weeks (TRA, 16 m/min, 60 min/day, 5 days/week), and treadmill-running trained for 8 weeks followed by 4 weeks of detraining (DET). At sacrifice, left ventricular myocytes were isolated enzymatically, and resting cell length, width, and cell shortening after stimulation at a frequency of 1 Hz (~25°C) were measured. Cell length was greater in TRA than in SED-8 (161.30 ± 1.01 vs 156.10 ± 1.02 µm, P < 0.05, 667 vs 618 cells, respectively) and remained larger after detraining. Cell width and volume were unaffected by either exercise training or detraining. Cell length to width ratio was higher in TRA than in SED-8 (8.50 ± 0.08 vs 8.22 ± 0.10, P < 0.05) and was maintained after detraining. Exercise training did not affect cell shortening, which was unchanged with detraining. TRA cells exhibited higher maximum velocity of shortening than SED-8 (102.01 ± 4.50 vs 82.01 ± 5.30 µm/s, P < 0.05, 70 cells per group), with almost complete regression after detraining. The maximum velocity of relengthening was higher in TRA cells than in SED-8 (88.20 ± 4.01 vs70.01 ± 4.80 µm/s, P < 0.05), returning to sedentary values with detraining. Therefore, exercise training affected left ventricle remodeling in SHR towards eccentric hypertrophy, which remained after detraining. It also improved single left ventricular myocyte contractile function, which was reversed by detraining.

Exercise training and detraining modify the morphological and mechanical properties of single cardiac myocytes obtained from spontaneously hypertensive rats

We determined the effects of exercise training and detraining on the morphological and mechanical properties of left ventricular myocytes in 4-month-old spontaneously hypertensive rats (SHR) randomly divided into the following groups: sedentary for 8 weeks (SED-8), sedentary for 12 weeks (SED-12), treadmill-running trained for 8 weeks (TRA, 16 m/min, 60 min/day, 5 days/week), and treadmill-running trained for 8 weeks followed by 4 weeks of detraining (DET). At sacrifice, left ventricular myocytes were isolated enzymatically, and resting cell length, width, and cell shortening after stimulation at a frequency of 1 Hz (~25°C) were measured. Cell length was greater in TRA than in SED-8 (161.30 ± 1.01 vs 156.10 ± 1.02 μm, P < 0.05, 667 vs 618 cells, respectively) and remained larger after detraining. Cell width and volume were unaffected by either exercise training or detraining. Cell length to width ratio was higher in TRA than in SED-8 (8.50 ± 0.08 vs 8.22 ± 0.10, P < 0.05) and was maintained after detraining. Exercise training did not affect cell shortening, which was unchanged with detraining. TRA cells exhibited higher maximum velocity of shortening than SED-8 (102.01 ± 4.50 vs 82.01 ± 5.30 μm/s, P < 0.05, 70 cells per group), with almost complete regression after detraining. The maximum velocity of relengthening was higher in TRA cells than in SED-8 (88.20 ± 4.01 vs70.01 ± 4.80 μm/s, P < 0.05), returning to sedentary values with detraining. Therefore, exercise training affected left ventricle remodeling in SHR towards eccentric hypertrophy, which remained after detraining. It also improved single left ventricular myocyte contractile function, which was reversed by detraining.

Hair interior defect in AKR/J mice.

BACKGROUND: All AKR/J mice have a subtle defect that involves malformation of the central portion of hair fibres that is best visualized under white and polarized light microscopy. AIMS: This study sought to characterize the clinical and ultrastructural features of the hair interior defect (HID) phenotype and to determine the chromosomal localization of the hid mutant gene locus. METHODS: White and polarized light microscopy combined with scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to characterize the HID phenotype. Complementation testing and gene-linkage studies were performed to map the locus. RESULTS: Using SEM, the hair-fibre structure on the surface was found to be similar to hairs obtained from normal BALB/cByJ+/+and C57BL/6 J+/+mice. There were also no differences in sulphur content. TEM revealed degenerative changes in the medulla similar to that seen by light microscopy. This autosomal recessive mutation is called HID (locus symbol: hid). We mapped the hid locus to the distal end of mouse chromosome 1. No genes reported to cause skin or hair abnormalities are known to be within this interval except for the lamin B receptor (Lbr), which had been excluded previously as the cause of the hid phenotype in AKR/J mice. CONCLUSION: A potentially novel gene or known gene with a novel phenotype resides within this interval, which may shed light on human diseases with defects in the inner structure of the hair fibre.

Expression of terminal differentiation proteins defines stages of mouse mammary gland development.

Immunohistochemical analysis using paraffin-embedded specimens is the method of choice to evaluate protein expression at a cellular level while preserving tissue architecture in normal and neoplastic tissues. Current knowledge of the expression of terminal differentiation markers in the mouse mammary gland relies on the evaluation of frozen tissues by use of immunofluorescence. We assessed changes in patterns of expression of terminal differentiation markers throughout the development of the mouse mammary gland in paraffin-embedded tissues. The expression of alpha-smooth muscle actin (SMA) and keratins (K) 5, 8/18, and 14 was influenced by the development stage of the mammary gland. Expression of K5 and SMA was restricted to basal cells. Keratin 14 was consistently expressed by mammary basal cells, and was detected in scattered luminal cells from 13.5 days after conception through puberty. Labeling for K8/18 of luminal cells was heterogeneous at all times. Heterogeneous expression patterns in luminal cells suggest this layer has cells with a variety of biological functions. The absence of K6 expression at any stage of the development of the mammary gland was confirmed by use of reverse transcriptase-polymerase chain reaction analysis, which indicates that this intermediate filament is not a marker of the mammary gland stem cell. Finally, consistent with results of earlier studies, keratins 1, 10, 13, and 15, and filaggrin, involucrin, and loricrin were not detected at any stage of mammary gland development.