Pharmacokinetic of florfenicol in pulmonary epithelial lining fluid of swine and effects of anesthetic agent on drug plasma disposition kinetics / Farmacoqu'imica de florfenicol em fluido de epitélio pulmonar de suínos e efeitos de agente anestésico em cinética de droga em plasma

The primary objective of the current study was to compare the pharmacokinetic (PK) of florfenicol (FFL) in pulmonary epithelial lining fluid and the plasma in swine. The second objectives were to evaluate the effect of anesthesia with ketamine and propofol on the PK of FFL in plasma. Bronchoaveolar lavage was utilized for quantification of PELF volume and the urea dilution method was used to determine the concentration of FFL in PELF. FFL was administered intramuscularly (IM) to swine in a single dose of 20mg/kg body weight. The main PK parameters of FFL in plasma and PELF were as follows: the area under the concentration-time curve, maximal drug concentration, elimination half-life and mean residence time were 69.45±4.36 vs 85.03±9.26µg·hr/ml, 4.65±0.34 vs 5.94±0.86µg/ml, 9.87±1.70 vs 10.69±1.60hr and 12.75±0.35 vs 14.46±1.26hr, respectively. There was no statistically significant difference between the PK profiles of FFL for the anesthetized and unanesthetized pigs. This study suggest that (i) FFL penetrated rapidly into the pulmonary and the drug concentration decay faster in plasma than in the pulmonary, (ii) the PK profile of FFL in swine was not interfered after administration of anesthetic agent.(AU)

O objetivo primário desse estudo foi comparar a farmacocinética de florfenicol (FFL) em fluido epitelial pulmonar à farmacocinética (PK) de FFL em plasma suíno. O segundo objetivo foi avaliar o efeito de anestesia com ketamina e propofol no PK de FFL em plasma. Lavagem broncoalveolar foi utilizada para quantificar volume de fluido epitelial pulmonar (PELF) e método de diluição de uréia para determinar FFL em PELF. Injeção de FFL foi administrada intramuscular a suínos em dose única de 20mg/kg de peso corporal. Os principais parâmetros de PK em FFL em plasma e PELF foram os seguintes: a área sob a curva de concentração-tempo, concentração máxima da droga, eliminação de meia-vida e média de tempo de permanência foram 69,45±4,36 vs 85,03±9,26µg·hr/ml, 4,65±0,34 vs 5,94±0,86µg/ml, 9,87±1,70 vs 10,69±1,60hr e 12,75±0,35 vs 14,46±1,26hr, respectivamente. Não houve diferença estatisticamente significante entre os perfis de PK de FFL para os porcos anestesiados e não anestesiados. Esse estudo sugere que (i) FFL penetrou rapidamente no pulmão e concentração da droga sofre queda mais veloz em plasma que líquido pulmonar, (ii) o perfil de PK de FFL em suínos não modificou após administração de agente anestésico.(AU)

BPI-fold (BPIF) containing/plunc protein expression in human fetal major and minor salivary glands

Abstract The aim of this study was to determine expression, not previously described, of PLUNC (palate, lung, and nasal epithelium clone) (BPI-fold containing) proteins in major and minor salivary glands from very early fetal tissue to the end of the second trimester and thus gain further insight into the function of these proteins. Early fetal heads, and major and minor salivary glands were collected retrospectively and glands were classified according to morphodifferentiation stage. Expression of BPI-fold containing proteins was localized through immunohistochemistry. BPIFA2, the major BPI-fold containing protein in adult salivary glands, was detected only in the laryngeal pharynx; the lack of staining in salivary glands suggested salivary expression is either very late in development or is only in adult tissues. Early expression of BPIFA1 was seen in the trachea and nasal cavity with salivary gland expression only seen in late morphodifferentiation stages. BPIFB1 was seen in early neural tissue and at later stages in submandibular and sublingual glands. BPIFA1 is significantly expressed in early fetal oral tissue but BPIFB1 has extremely limited expression and the major salivary BPIF protein (BPIFA2) is not produced in fetal development. Further studies, with more sensitive techniques, will confirm the expression pattern and enable a better understanding of embryonic BPIF protein function.

Hypoxia Increases Epithelial Permeability in Human Nasal Epithelia

PURPOSE: The nasal mucosa is the first site to encounter pathogens, and it forms continuous barriers to various stimuli. This barrier function is very important in the innate defense mechanism. Additionally, inflammation of the nasal sinus is known to be a hypoxic condition. Here, we studied the effect of hypoxia on barrier function in normal human nasal epithelial (NHNE) cells. MATERIALS AND METHODS: The expression levels of various junction complex proteins were assessed in hypoxia-stimulated NHNE cells and human nasal mucosal tissues. We performed real-time polymerase chain reaction analysis, western blotting, and immunofluorescence assays to examine differences in the mRNA and protein expression of ZO-1, a tight junction protein, and E-cadherin in NHNE cells. Moreover, we evaluated the trans-epithelial resistance (TER) of NHNE cells under hypoxic conditions to check for changes in permeability. The expression of ZO-1 and E-cadherin was measured in human nasal mucosa samples by western blotting. RESULTS: Hypoxia time-dependently decreased the expression of ZO-1 and E-cadherin at the gene and protein levels. In addition, hypoxia decreased the TER of NHNE cells, which indicates increased permeability. Human nasal mucosa samples, which are supposed to be hypoxic, showed significantly decreased levels of ZO-1 and E-cadherin expression compared with control. CONCLUSION: Our results demonstrate that hypoxia altered the expression of junction complex molecules and increased epithelial permeability in human nasal epithelia. This suggests that hypoxia causes barrier dysfunction. Furthermore, it may be associated with innate immune dysfunction after encountering pathogens.

Keratinized versus non-keratinized preputial flap onlay urethroplasty: does it make any difference in the histological analysis? An experimental study in rabbits

Purpose To compare the histological characteristics of keratinized versus non-keratinized onlay island flaps in an experimental rabbit model. Materials and Methods Sixteen male rabbits were randomly allocated into two experimental groups: keratinized and non-keratinized onlay island flaps. A defect was created in the ventral aspect of the penile urethra. In the keratinized group, a longitudinal island flap was harvested from the external prepuce and rotated to cover the urethral defect. In the non-keratinized group a transverse island flap was harvested from the inner prepuce. The animals were sacrificed after 2, 4, 8 and 12 weeks. Results The flaps were viable in all animals, and no deaths were associated with the procedure. Two urethrocutaneous fistulas were identified, one in each experimental group. A similar pattern of fibrosis was identified in both groups. The keratinized epithelium of the external prepuce kept its histological aspect and keratin production. Both keratinized and non-keratinized groups presented a slight decrease on the epithelial thickness, however without a statistically significant difference between groups. Conclusions In this short-term rabbit model, we observed that the stratified squamous keratinized epithelium from the external prepuce kept its keratin production. There was no statistical influence of the flap type on the mean epithelial thickness. .

Determinaçäo dos receptores de estrogênio pelo método imunocitoquímico em fragmentos do epitélio de neovaginas de mulheres portadoras de agenesia vaginal / Determination of estrogen receptors by immunocitochemical method in fragments of epithelium of neovaginas in women with vaginal agenesis

OBJETIVOS: Observar as transformaçoes que ocorrem em fragmentos de membrana amniótica que foram utilizados para a confecçao de neovaginas em pacientes portadoras de agenesia útero-vaginal. CASUISTICA E METODOLOGIA: Foram 26 pacientes com agenesia utero-vaginal onde utilizou-se a técnica proposta por McIndoe. Para análise do epitélio da neovagina empregou-se método visando a determinaçao dos receptores de estrgênio citoplasmáticos (REc). Todos estes fragmentos de epitélio foram processados por método imunocitoquimico PAP (peroxidase x antiperoxidase). RESULTADOS: Estes receptores estrogênicos foram determinados em diversos graus de intensidade na camada profunda (CP), camada intermediária (CI) e na camada superficial (CS) dos epitélios de neovaginas. CONCLUSOES: O resultado obtido quanto ao grau de intensidade dos REc nas diversas camadas do epitélio vaginal de mulheres no menacme sao estatisticamente semelhantes e comparáveis no grau de intensidade aos fragmentos obtidos de epitélio de neovaginas confeccionadas com membrana amniótica.

Estudo comparativo das proteínas p53, PCNA, Ki-67 e das regiöes organizadoras nucleolares (NORs) no epitélio de revestimento da mucosa próximo ao carcinoma epidermóide de boca / p53, PCNA, Ki-67 and NORs in lining epilhelium adjacent to squamous cell carcinoma of human oral mucosa

O epitélio de revestimento da mucosa adjacente aos carcinomas epidermóides pode apresentar alteraçöes morfológicas e histoquímicas representativas da carcinogênese precoce. Essas alteraçöes podem ser expressäo de um processo de "campo de cancerizaçäo". A avaliçäo histopatológica dessas alteraçöes é difícil, subjetiva e nem sempre é uma indicaçäo confiável da progressäo para carcinoma invasivo. O objetivo deste trabalho foi estudar a expressäo do p53, PCNA, Ki-67 e NORs no epitélio de revestimento da mucosa próximo a 26 carcinomas epidermóides de boca, verificando a correlaçäo desses marcadores com grau de atipia epitelial e a correlaçäo entre os mesmos. Foi utilizada a técnica imuno-histoquímica e histoquímica em tecidos rotineiramente fixados e processados, empregando-se anticorpos anti-p53, anti-Ki-67 e a coloraçäo pela prata coloidal, AgNOR. Nós näo encontramos correlaçäo de nenhum dos marcadores com o grau de atipia epitelial. Correlaçäo foi observada apenas entre o PCNA e Ki-67. Nós sugerimos que as alteraçöes relacionadas a estes marcadores podem preceder as alteraçöes morfológicas no epitélio adjacente aos carcinomas epidermóides de boca, e que o estudo dos mesmos podem ajudar na decisäo sobre o manejamento da lesäo

Expression of HLA-DR antigen in large bowel carcinoma

One hundred large bowel carcinomas were studied immunohistochemically with regard to expression of HLA-DR antigen (DR). One or two sections from each tumor including surrounding normal mucosa were examined by a semiquantitative counting system for tumor cells and mucosal and stromal infiltrates of lymphocytes and mononuclear cells (MNCs) with DR expression and the results were applied Chi-square test. The rate of presence of DR positive (DR+) lymphocytes in lymphoid nodules and DR+ lymphocytes/ MNC in the adjacent mucosa and stroma in DR+ carcinoma (50%) was higher (P < 0.01) than in DR- carcinoma (21.9%). Thirty-six carcinomas (36%) were DR+. Three (75%) out of 4 DR+ poorly differentiated carcinomas and six (20%) out of 30 DR+ moderately differentiated carcinomas showed homogeneously strong DR+ expression. There was tendency for poorly differentiated carcinoma to be more homogeneous DR+ expression. According to Dukes' stage, four (80%) out of 5 carcinomas in Dukes' stage D were DR-. An increased infiltration of lymphocytes/MNCs into adjacent mucosa and stroma in large bowel carcinomas is possibly related with DR expression by carcinoma. From the results of this study, we postulated as follows: 1) DR+ tumor cells may act as antigen-presenting cells, 2) They may have an inhibitory effect for distant metastasis, 3) Poorly differentiated carcinoma expressed more DR+ homogeneously.

Studies on nonesterified fatty acids in rat intestinal cell membranes.

Lipid composition of total membrane fractions prepared from scraped rat intestinal mucosa and isolated epithelial cells were compared. Membranes prepared from mucosa had four times higher nonesterified fatty acids (NEFA) as compared to the epithelial cell membranes. Cholesterol and phospholipid contents were similar in both the membrane preparations but triglyceride content was high and di- and monoglyceride were low in epithelial cell membranes as compared to the mucosal membranes. Inclusion of p-bromophenacyl bromide, a phospholipase inhibitor, in the intestinal lumen wash solution and homogenizing buffer did not reduce the NEFA content of the scraped mucosal membranes whereas inclusion of diethyl p-nitrophenyl phosphate, a lipase inhibitor reduced it by 40%. These results suggest that NEFA are normal constituent of intestinal cell membranes.

Immunohistochemical localization of insulin-like materials in antral gastric mucosa and intestinal epithelial cells of the turtles Chrysemys dorbigni and Phrynopshilarii

Immunoreactive insulinwas demonstrated immunohistochemically with antibodies to human and porcine insulin by the avidin-biotin-peroxidase complex method in open-type gastrointestinal cells from sections of the antral stomach and of the upper, midle and lower intestine of the turtles Chrysemys dorbigni and Phrynops hilarii.In both species the concentration of cells positive for insulin-like material was higher in the gastric antrummthan in the gut.The localization of insulin-like material in gastrointestinal mucosal cells of turtles is an unusual finding among vertebrates, because the insulin-containing cells migrate from the mucosal epithelium of the intestine early in vertebrate evolution to the acinar pancreas.The chemical nature of the gastrointestinal insulin-like material and its physiological role remainm to be determined

Aspectos histoquímicos do muco do epitélio de revestimento do oviduto de coelha / Cytochemical observations on the nature of the mucin of the surface epithelium of the rabbit oviduct

Procurou-se detectar, por intermédio de métodos histoquímicos a natureza carboidrática do muco elaborado pelas células secretoras do epitélio que reveste as porçöes do infundíbulo, ampola e istmo do oviduto de coelha em anestro. Com base nos resultados obtidos, foi possível concluir que o oviduto de coelha é revestido por uma camada de muco. Este muco está representado por uma fraçäo neutra e outra ácida. Com relaçäo ao componente ácido, encontramos que as três porçöes do oviduto estäo revestidas por carboximucina, sendo que no infundíbulo encontramos também uma sialomucina e na ampola e no istmo uma sulfomucina. Os autores procuram relacionar estes dados com aspectos fisiológicos