RESUMO
Hypoalbuminemia (HA) is frequently observed in systemic inflammatory diseases and in liver disease. However, the influence of HA on the pharmacokinetics and toxicity of compounds with high plasma albumin binding remained insufficiently studied. The 'lack-of-delivery-concept' postulates that HA leads to less carrier mediated uptake of albumin bound substances into hepatocytes and to less glomerular filtration; in contrast, the 'concept-of-higher-free-fraction' argues that increased concentrations of non-albumin bound compounds facilitate hepatocellular uptake and enhance glomerular filtration. To address this question, we performed intravital imaging on livers and kidneys of anesthetized mice to quantify the spatio-temporal tissue distribution of the mycotoxin ochratoxin A (OTA) based on its auto-fluorescence in albumin knockout and wild-type mice. HA strongly enhanced the uptake of OTA from the sinusoidal blood into hepatocytes, followed by faster secretion into bile canaliculi. These toxicokinetic changes were associated with increased hepatotoxicity in heterozygous albumin knockout mice for which serum albumin was reduced to a similar extent as in patients with severe hypoalbuminemia. HA also led to a shorter half-life of OTA in renal capillaries, increased glomerular filtration, and to enhanced uptake of OTA into tubular epithelial cells. In conclusion, the results favor the 'concept-of-higher-free-fraction' in HA; accordingly, HA causes an increased tissue uptake of compounds with high albumin binding and increased organ toxicity. It should be studied if this concept can be generalized to all compounds with high plasma albumin binding that are substrates of hepatocyte and renal tubular epithelial cell carriers.
Assuntos
Hipoalbuminemia , Micotoxinas , Ocratoxinas , Animais , Hipoalbuminemia/metabolismo , Rim/metabolismo , Fígado/metabolismo , Camundongos , Micotoxinas/metabolismo , Ocratoxinas/química , Albumina Sérica/metabolismo , Distribuição TecidualRESUMO
The current study investigated the sublingual floor of Rahmani sheep (Ovis aries). Samples from nine healthy adult sheep have been analysed using morphometrical, scanning electron microscopic (SEM), and histological examination. The sublingual floor of the sheep was formed of a rostral prefrenular part (spatula-shaped) and two lateral sublingual recesses. Right and left sublingual caruncles were asymmetrical in length and each one had a serrated border, divided into three papillae. At higher magnifications, the three papillae of the sublingual caruncle's edge were variable in shape, with other two papillae were demonstrated underneath the caruncle. Each sublingual recess had a sublingual fold (plica sublingualis) extended from the level of frenulum linguae till the glossopalatine arch, bordered with caudolaterally directed papillae till the level of first lower molar cheek teeth. The sublingual salivary glands were mixed (seromucoid) type. The glandular lobule consisted of mucous acini and sporadic serous acini, as well as the presence of some mucous acini capped by acidophilic cells, serous demilunes. The mucous acinus was formed of pyramidal mucous cells with pale stained cytoplasm and basally located nuclei. Two ducts; major sublingual and submandibular ducts were observed within the submucosa of the sublingual caruncle. The sublingual ductal pseudostratified columnar epithelium was interspersed by more goblet cells than that of the submandibular duct. Collagen fibres around the glandular lobules, intralobular and interlobular excretory ducts as well as the connective core of the papillae were noticed. By SEM, two epithelium-lined pits on the surface of the sublingual floor mucosa caudal to the central incisive teeth were termed orobasal organ. As the first study to give a comprehensive analysis of the sheeps' sublingual floor, this one serves as a baseline for future clinical studies.
Assuntos
Carneiro Doméstico , Papilas Gustativas , Animais , Ovinos , Microscopia Eletrônica de Varredura/veterinária , Glândula Sublingual/anatomia & histologia , LínguaRESUMO
Macroscopical and histological analysis of the skin is fundamental in both human and veterinary forensic investigations. However, databases of differential skin histology of various animal species are rare. The aim of the present study is to identify species-specific differential histological features of the skin that could be used in forensic investigations including animal identification. For this purpose, skin specimens were collected from the neck region of various farm animals including buffalo, cow, camel, sheep, goat, dog, and donkey, and were processed for histological analysis. Our comparative analysis revealed specific histological features in the skin that could differentiate between the studied animal species. The epidermis layer of the skin was very thick in buffalo, intermediate in cow, sheep, goat, dog, and donkey, but very thin in camel. The papillomatous epidermis was very frequent in buffalo, but very rare in cow. In the dermis layer of the skin, four structures were located which showed differential features between the studied animal species: the papillary layer, which was thick in buffalo, camel, sheep, dog, and donkey but thin in cow and goat. The sweat glands, which were few in buffalo, cow, goat, and dog, but numerous and deeply located in the dermis of sheep; they were individually located in all studied animals except in camel and donkey they were arranged in clusters. The hair follicles were characteristic for the skin of sheep as they were present at two different levels in the dermis with simple and compound hair follicles. The sebaceous glands were large and multi-lobular in buffalo, but small and uni-lobular in cow and camel. The hypodermis layer of the skin was very thick in sheep and goat in contrast to all other analyzed animals. In conclusion, the present study provides comprehensive information on the differential histological features of the skin of seven different domestic animal species that could be used as a key in forensic investigations.
RESUMO
The present study investigated the hard palate of Rahmani sheep (Ovis aries). Samples from nine healthy adult male sheep were investigated using morphometrical, histological and scanning electron microscopic examination. Morphologically, the hard palate was elongated, narrow rostrally, and wide caudally. The incisive papilla was heart-shaped, flanked on both sides by a groove on which the nasopalatine duct opened. The palatine raphe was in the form of a groove that contained a ridge caudally. On both sides of the raphe, 13-15 pairs of palatine ridges were present and mainly occupying the narrow part. The wide part had a rough part that contains few ridges rostrally and a smooth part caudally. Histologically, the incisive papilla and palatine ridges were lined by a keratinized stratified squamous epithelium resting on a dense layer of lamina propria. The incisive papilla characterized by the presence of seromucoid salivary glands and hyaline cartilage fragments in the lamina propria. The salivary glands became abundant and well-developed in the wide part till the end of hard palate. All palatine salivary glands were Alcian blue-periodic acid-Schiff positive. By scanning electron microscopy, numerous gland openings were scattered on the surface of the palatine ridges. In conclusion, the hard palate of Rahmani sheep presented characteristic features, which may be related to the species differences, feeding behavior, and possible functional adaptations. This is the first study to report the presence of cartilaginous segments and salivary glands in the incisive papilla and provide detailed descriptions of the Rahmani sheep hard palate.
Assuntos
Palato Duro , Carneiro Doméstico , Animais , Elétrons , Masculino , Microscopia Eletrônica de Varredura , Mucosa , OvinosRESUMO
The present study investigated the morphology of the palate of rabbit (Oryctolagus cuniculus). Samples from 12 healthy adult rabbits were examined by gross observation, morphometry, scanning electron and light microscopy. The hard palate was elongated and narrowed rostrally. The incisive papilla appeared as a diamond-shaped prominence flanked on both sides by a groove on which a slit-like opening of the nasopalatine duct opened. The palatine raphe was in the form of a groove. On either side of the raphe, 14-16 palatine ridges were present. The direction of these ridges differed according to their position. An incomplete (short) palatine ridge was occasionally present at the caudal part of the hard palate. Several gland openings were scattered on the surface of the palatine ridges. The soft palate extended to about the middle of epiglottis caudally. Its ventral surface had numerous thin transverse mucosal folds separated by furrows, and several openings of glands. Histologically, the incisive papilla, palatine ridges, and soft palate were lined by a parakeratinized stratified squamous epithelium resting on a dense connective layer of lamina propria. The degree of keratinization and the thickness of the lamina propria decreased caudally. Seromucoid glands were present in the rostral and caudal parts of the hard palate, as well as in the soft palate. In conclusion, the palate of rabbit presented characteristic features suggesting functional adaptations for their herbivores diet. Studying the morphological characteristics of the hard and soft palate of rabbits will help veterinary practitioners to investigate pathology malformations and diseases of the oral cavity.
Assuntos
Mucosa , Palato , Animais , Epiglote , Epitélio , Microscopia Eletrônica de Varredura , Mucosa Bucal , CoelhosRESUMO
The present study investigated the morphological, as well as the histological features of the Egyptian red fox's palate, in addition to the three-dimensional characteristics of the connective tissue papillae (CTP) of the palate by scanning electron microscopy (SEM). The hard palate was narrow rostrally and its width increased caudally. The maximum width was located at the caudal border of the upper fourth premolar tooth. The incisive papilla was represented by a rounded median elevation surrounded on each side by a groove on which the oral openings of the incisive ducts opened. The rostral part of the hard palate had 9-10 caudally concave transverse palatine ridges while the caudal part appeared smooth without ridges. The palatine raphe was indistinct rostrally but formed a groove caudally. By SEM, the palatine ridges had low projections. Different microplicae systems were present on the epithelial surface of the incisive papilla, palatine rugae, interrugal areas, and the smooth part. The CTP of the incisive papilla, palatine ridges, and soft palate were conical-shaped, cylindrical-shaped, and parallel serrated ridges, respectively. Histologically, the hard palate was lined by a cornified stratified squamous epithelium resting on a dense connective layer of lamina propria while the soft palate was lined by a noncornified stratified squamous epithelium. The palatine salivary glands were present in the smooth part of the hard palate and the soft palate. The information presented in the current study might serve as a reference guide for the interpretation of pathological conditions of the palate of red fox.
Assuntos
Raposas , Mucosa Bucal , Animais , Tecido Conjuntivo , Egito , Microscopia Eletrônica de Varredura , Palato MoleRESUMO
The aim was to determine whether probiotics-feeding can affect the expression and localization of avian beta defensins (AvBDs) and proinflammatory cytokines in response to Salmonella minnesota lipopolysaccharide (LPS) in the gastrointestinal tract. One-day-old male Chunky broiler chicks were fed with or without 0.4% probiotics for 7 days (P-group and non-P-group, respectively). Then, they were orally challenged with no LPS (0-LPS), 1 µg LPS (1-LPS), or 100 µg LPS (100-LPS) (n = 5, each), in experiment 1, and with no LPS and 1 µg LPS (n = 6, each) in experiment 2. Five hours after LPS challenge, the proventriculi and ceca were collected. A total of seven and eight AvBDs were identified in proventriculus and cecum, respectively. The density of ir-AvBD12 in the surface epithelium of proventriculus increased in the P-group in response to 1-LPS and 100-LPS stimulation. In experiment 1, the expression of two AvBDs in the proventriculus and six AvBDs in the cecum of 1-LPS chicks was higher in P-group than in the non-P-group. Results of experiment 2 showed similar tendency to experiment 1. These results suggest that probiotics-feeding may enhance the immunodefense system mediated by AvBDs but not by cytokine, against infection by Gram-negative bacteria.
Assuntos
Peptídeos Antimicrobianos , Galinhas/imunologia , Imunomodulação , Probióticos , Animais , Peptídeos Antimicrobianos/imunologia , Ceco/imunologia , Lipopolissacarídeos , Masculino , SalmonellaRESUMO
Mouse models of non-alcoholic fatty liver disease (NAFLD) are required to define therapeutic targets, but detailed time-resolved studies to establish a sequence of events are lacking. Here, we fed male C57Bl/6N mice a Western or standard diet over 48 weeks. Multiscale time-resolved characterization was performed using RNA-seq, histopathology, immunohistochemistry, intravital imaging, and blood chemistry; the results were compared to human disease. Acetaminophen toxicity and ammonia metabolism were additionally analyzed as functional readouts. We identified a sequence of eight key events: formation of lipid droplets; inflammatory foci; lipogranulomas; zonal reorganization; cell death and replacement proliferation; ductular reaction; fibrogenesis; and hepatocellular cancer. Functional changes included resistance to acetaminophen and altered nitrogen metabolism. The transcriptomic landscape was characterized by two large clusters of monotonously increasing or decreasing genes, and a smaller number of 'rest-and-jump genes' that initially remained unaltered but became differentially expressed only at week 12 or later. Approximately 30% of the genes altered in human NAFLD are also altered in the present mouse model and an increasing overlap with genes altered in human HCC occurred at weeks 30-48. In conclusion, the observed sequence of events recapitulates many features of human disease and offers a basis for the identification of therapeutic targets.
Assuntos
Carcinoma Hepatocelular/patologia , Dieta Ocidental/efeitos adversos , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Modelos Animais de Doenças , Progressão da Doença , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BLRESUMO
This study was conducted to provide comprehensive information on the anatomical and histological features of the upper (UL) and lower (LL) lips of Rahmani sheep by gross examination, morphometric analysis in addition to Light and scanning electron microscope (SEM). Samples from normal healthy adult male sheep heads were collected directly after slaughtering. UL and LL were dissected, and specimens were collected for both light and SEM. The UL was longer approximately by one-fold and thicker by one-fold at the median and the oral angle areas, and by one- and half-folds at the paramedian area than the LL. The free border of both lips was characterized rostrally by the presence of labial projections. By SEM the edges of the inner aspect of the lips and of the philtrum were distinguished by labial projections. These projections which surrounding the philtrum subdivided into polygonal areas with numerous keratinized scales especially at the apical parts which increased dorsally toward the nostril. Most of the openings of the upper labial salivary glands were volcanic crater-shaped while that of the lower labial salivary glands were various shapes; round folded margin, rosette and whirlpool shaped. Histologically, the shape of the projection or papillae differs at the median and paramedian areas of the UL than the LL. However, there was no differences near the oral angle area. In conclusion, the shape, size and amount of keratinization of the papillae may offer efficiency to the lips during feeding process.
RESUMO
The aim of this study was to determine whether probiotic-feeding affected the expression of cathelicidins (CATHs), a major family of antimicrobial peptides, in response to lipopolysaccharides (LPS) challenge in the proventriculus and cecum of broiler chicks. One-day-old male Chunky broiler chicks were fed with or without 0.4% probiotics for 7 days (P-group and non-P-group, respectively). Then, they were orally challenged with no LPS (0-LPS), 1 µg LPS (1-LPS), or 100 µg LPS (100-LPS) (n=5 in all groups) in Experiment 1, and with no LPS or 1 µg LPS (n=6 in all groups) in Experiment 2. Five hours after LPS challenge, the proventriculi and ceca were collected to analyze CATHs expression. Expression of CATHs was examined at first by reverse transcription-polymerase chain reaction (RT-PCR) using the 0-LPS chicks of non-P-group. The differences in CATHs expression upon probiotics-feeding and LPS were analyzed by real time-PCR. All four CATHs (CATH1, 2, 3 and 4) were expressed in the proventriculus and cecum of chicks. In the proventriculus, the expression of CATHs after LPS challenge did not show significant differences between non-P and P-groups in Experiment 1 and 2. In the cecum, the interactions of the effects of probiotics and LPS on the expression of CATH2 in Experiment 1 and CATH1 and 2 in Experiment 2 were significant, and their expression in 1-LPS chicks was higher in P-group than in non-P-group. However, CATH3 and 4 did not show any significant differences between non-P- and P-groups challenged with LPS. These results suggest that probiotics-feeding may stimulate the immunodefense system mediated by CATH2 and possibly CATH1 against infection by Gram-negative bacteria in the cecum.