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1.
REASONS FOR PERFORMING STUDY: Experimental induction of equine laminitis with a reliable and clinically relevant model should facilitate understanding of the disease. Successful induction with oligofructose (OF) could link pasture consumption to laminitis. OBJECTIVES: To determine whether alimentary administration of OF induces laminitis. METHODS: Twelve horses were dosed with OF and 6 received a sham (placebo) treatment. Clinical observations were made and blood collected at 4 h intervals over a 48 h study period. Stained sections of the hoof wall lamellae, examined by light microscopy, were graded for laminitis severity. RESULTS: All horses administered OF, but no sham-treated controls, developed clinical and histological laminitis. CONCLUSIONS AND POTENTIAL RELEVANCE: Alimentary overload with OF is a valid induction model for studying the pathogenesis of laminitis. A link is therefore established between field cases of laminitis and pasture fructan content. 相似文献
2.
Reason for performing study: The role of matrix metalloproteases (MMPs) and the timeline of proteolysis during laminitis development are incompletely understood. Objectives: To determine the temporal progression of selected MMPs and protease regulators during laminitis development. Methods: Five clinically normal Standardbred horses received, via nasogastric intubation, an oligofructose (OF) bolus (10 g/kg bwt). Laminitis induction proceeded for 48 h followed by euthanasia. Lamellar biopsies were obtained prior to dosing and at intervals during the treatment period for analysis (12, 18, 24, 30 and 36 h and at 48 h following euthanasia). Tissue samples were analysed by real‐time PCR, zymography and western blotting. Results: Activation of proMMP‐2 occurs either simultaneously or at least 12 h following lamellar basement membrane (BM) damage, while no activation of proMMP‐9 is seen during OF laminitis induction. Aggrecanase gene expression increased initially at 12–18 h post OF dosing, similar to BM changes. Gene expression of TIMP‐2, a MMP regulator, decreases during laminitis development. Conclusions: The MMP‐2/MT1‐MMP complex may not play a major role in initiating lamellar BM damage. Aggrecanase and TIMP‐2 gene expression appear related to BM lamellar changes. Potential relevance: MMPs, historically thought to cause laminitis, do not appear to play an initiating role in the lamellar lesion. Other host derived proteases and degradation of alternative lamellar matrix components need to be considered. 相似文献
3.
Reasons for performing study: The timing of lamellar basement membrane (BM) changes occurring during laminitis development is incompletely understood. Objectives: To determine the temporal progression of lamellar BM changes and whether laminin‐332 (Ln‐332) γ2 cleavage products are generated during laminitis development. Methods: Eight clinically normal Standardbred horses were allocated into treatment (n = 5) or sham (n = 3) groups. The treatment group received, via nasogastric intubation, an oligofructose (OF) bolus (10 g/kg bwt) while the sham group was given water. Laminitis induction proceeded for 48 h followed by euthanasia. Lamellar biopsies were obtained prior to dosing and at intervals during the treatment period for analysis (at 12, 18, 24, 30 and 36 h and at 48 h following euthanasia). Results: Changes in lamellar collagen type IV and Ln‐332 were first observed at 12 h post dosing. A unique pattern of reactivity for the Ln‐332 γ2 antibody D4B5 occurred, in which reactivity was observed only in lamellar tissue affected by laminitis. No bioactive Ln‐332 γ2 proteolytic fragments were detected in lamellar samples. Conclusions: Basement membrane changes occurred early during the laminitis process. Direct Ln‐332 γ2 cleavage to release biologically active products did not appear to occur. Thus loss of stability or protein interaction of the BM is probably responsible for the γ2 specific reactivity observed. Potential relevance: Basement membrane changes may a first step in lamellar failure occurring prior to detection with conventional methods. Thus, more sensitive detection methods of BM changes are required to study laminitis development. 相似文献
4.
Reasons for performing study: The histopathology of laminitis during its transition from the acute to the chronic phase has not been previously documented. Studying hoof lamellar tissues 7 days after induction of laminitis may provide insight into the intractable nature of the chronic phase of the disease. Objectives: To induce laminitis and investigate hoof wall lamellar tissues 7 days after dosing. Methods: Laminitis was induced using oligofructose in 6 normal Standardbred horses. The dorsal hoof lamellar tissues of these and 12 normal horses were processed and examined by light microscopy. Serial sections of a lamellar tip affected by laminitis were used to create a 3 dimensional reconstruction. Results: Transverse sections of dorsal hoof wall lamellae were significantly longer than normal. Many secondary epidermal lamellae were not connected to primary lamellae and existed as spherical or ovoid, discrete islands isolated in the lamellar dermis. The lamellar basement membrane was intact. Conclusions: Lamellar tissue has the ability to reorganise rapidly following an episode of acute laminitis. Although histopathological evidence of ongoing acute laminitis was absent by 7 days, there was marked disruption of lamellar architecture. Potential relevance: The architecture and subsequent strength of the resultant lamellar interface could be greatly influenced for the better by strategies that minimise mechanical displacement during the acute phase of laminitis. 相似文献
5.
The effects of acute lipopolysaccharide challenge on dairy goat liver metabolism assessed with 1HNMR metabonomics 
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下载免费PDF全文 L. F. Wang S. D. Jia G. Q. Yang R. Y. Liu G. Y. Yang M. Li H. S. Zhu Y. Y. Wang L. Q. Han 《Journal of animal physiology and animal nutrition》2017,101(1):180-189
We investigated the mechanisms mediating hepatic metabolic responses to an acute lipopolysaccharide (LPS) challenge in goats. Guanzhong dairy goats (15) were randomly divided into three groups: control (CTL, saline, 0.2 ml/kg BW), lower dose LPS (LPS‐L, 20 μg/kg BW) and higher dose LPS (LPS‐H, 40 μg/kg BW). All injections were administered intraperitoneally twice with a 24‐h interval. Forty‐eight hours after the first injection, blood samples were collected to extract plasma for biochemical analysis, and liver tissues were biopsied and stored in liquid nitrogen for metabonomics analysis. We found that plasma levels of alanine aminotransferase, aspartate aminotransferase and total bilirubin increased (p < 0.05) in both LPS‐treated groups, whereas plasma triglyceride, cholesterol, very low‐density lipoprotein, low‐density lipoprotein, high‐density lipoprotein, total protein and albumin levels markedly decreased (p < 0.05). The increased activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), levels of tumour necrosis factor α (TNF‐α), interleukin (IL)‐1β, IL‐6 and IL‐8 indicated hepatic injury and metabolic dysfunction in some degree. Using proton nuclear magnetic resonance (1H‐NMR) metabonomics and the Chenomx NMR suite database, 69 metabolites were detected and identified. Metabolic differences among the groups were determined with pattern recognition analyses using principal component analysis and supervised projection to latent structures discriminant analysis. Pattern recognition analysis distinguished and clustered the metabolite variables from the three groups, finding nine of 69 metabolites that differed significantly between two of the three groups: six from the LPS‐L or LPS‐H groups differed from CTL and three differed between LPS‐L and LPS‐H groups. These altered metabolites were closely connected with glucose, lipid and amino acid metabolic pathways in hepatocytes. Based on an analysis of these metabolites and their relevant pathways, the mechanisms and degree of hepatic injury were deduced. Therefore, the metabolic profile was used effectively to detect characteristic hepatic metabolites, discriminate metabolic changes induced by LPS, clarify the mechanisms for the resulting metabolic dysfunctions and provide efficient information to diagnose liver injury. 相似文献
6.
Systemic inflammation is a risk factor for laminitis in horses and precedes the onset of lameness in experimental models. We therefore hypothesized that whole-blood inflammatory cytokine expression would increase during the development of laminitis in a carbohydrate overload model. Blood samples were obtained from 14 horses undergoing laminitis induction with 10 g/kg oligofructose as part of another study. Samples were collected at 0, 8, 12, 16, 20, and 24 hours, and lameness evaluations were performed every 4 hours. Expression levels of interleukin-1β (IL-1β), IL-6, IL-8, IL-10, and tumor necrosis factor-α were measured in whole blood by using real-time PCR. IL-1β, IL-8, and IL-10 expression increased above baseline from 8 to 24 hours (P < .001), and IL-6 expression increased at 16 and 20 hours (P = .005). Expression of tumor necrosis factor-α did not change over time. All horses developed clinical laminitis between 12 and 24 hours. Increased mean IL-1β, IL-8, and IL-10 expression detected at 8 hours therefore preceded the onset of lameness. We conclude that peripheral leukocyte cytokine expression increases as systemic inflammation develops in an alimentary carbohydrate overload model of laminitis, and this precedes detection of lameness. Results support current recommendations to control the systemic inflammatory response in order to lower the risk of laminitis in horses. 相似文献
7.
Laminitis is known to involve deregulation of proteases and destruction of the lamellar basement membrane with the host inflammatory response also playing a role. Leukocyte infiltration has been well characterized in the black walnut model of laminitis induction, but not in carbohydrate induced models. Increased gene expression of multiple cytokines, including IL-6, has also been implicated in laminitis development. Using real time PCR, immunohistochemistry and zymography methods, we characterize leukocyte infiltration and IL-6 gene expression in oligofructose (OF) induced laminitis. As well, we use two in vitro models to investigate a role for IL-6 in protease regulation. Laminitis was induced in normal standardbred horses (n=5) by alimentary OF dosing and lamellar biopsies were obtained throughout the 48 h experimental period. Lamellar explants and keratinocytes were also isolated from clinically normal horses for in vitro experiments. We found infiltration of calprotectin-positive leukocytes (monocytes and neutrophils) at 18-24h post oligofructose dosing, while IL-6 gene expression was increased as early as 12h post dosing. Additionally, while we found that IL-6 did not cause significant BM damage in vitro, it did result in increased secreted proMMP-9 levels from lamellar explants. Thus, we find that leukocyte infiltration does occur during oligofructose-induced laminitis development, however, IL-6 gene expression in the lamellae may precede leukocyte infiltration. Additionally, we show IL-6 plays a role in increasing the level of proMMP-9 in vivo in a manner that does not involve keratinocytes. 相似文献
8.
Reasons for performing study: A previous preliminary study demonstrated the potential of distal limb cryotherapy (DLC) for preventing laminitis. Clinically, DLC must be effective for periods longer than 48 h and the preventive effect must extend beyond its discontinuation. Objectives: To evaluate the effect of DLC, applied during the developmental phase of induced laminitis, on the severity of clinical laminitis and lamellar histopathology 7 days after dosing. Methods: Eighteen normal Standardbred horses were divided into 3 groups of 6. Continuous cryotherapy was applied for 72 h to the distal limbs of the first group. The second and third groups were administered laminitis inducing doses of oligofructose and 72 h of cryotherapy applied (immediately after dosing) to the second group. After clinical assessment all horses were subjected to euthanasia 7 days after dosing and hoof lamellar tissues were harvested and analysed. Results: In the laminitis induced horses clinical lameness and laminitis histopathology was significantly reduced in horses that underwent 72 h of DLC compared with untreated controls. Cryotherapy alone produced no significant lameness or other ill effect. Conclusions: Continuous, medium‐ to long‐term (72 h) cryotherapy applied to the distal limbs of horses safely and effectively ameliorates the clinical signs and pathology of acute laminitis. Potential relevance: Pre‐emptive distal limb cryotherapy is a practical method of ameliorating laminitis in ill horses at risk of developing the disease. 相似文献
9.
Reasons for performing study: The pathophysiological events inhibited by prophylactic digital hypothermia that result in reduction of the severity of acute laminitis are unknown. Objectives: To determine if digital hypothermia inhibits lamellar inflammatory signalling during development of oligofructose (OF) induced laminitis. Methods: Fourteen Standardbred horses were given 10 g/kg bwt OF by nasogastric tube with one forelimb (CRYO) continuously cooled by immersion in ice and water and one forelimb (NON‐RX) at ambient temperature. Lamellae were harvested prior to the onset of lameness (24 h post OF administration, DEV group, n = 7) or at the onset of lameness (OG1 group, n = 7). Lamellar mRNA was purified and cDNA produced for real time‐quantitative PCR analysis of mRNA concentrations of cytokines (IL‐6, IL‐1β, IL‐10), chemokines (CXCL1, CXCL6, CXCL8/IL‐8, MCP‐1, MCP‐2), cell adhesion molecules (ICAM‐1, E‐selectin), COX‐2 and 3 housekeeping genes. Data were analysed (NON‐RX vs. CRYO, NON‐RX vs. archived control [CON, n = 7] lamellar tissue) using nonparametric tests. Results: Compared with CON, the OG1 NON‐RX had increased (P<0.05) lamellar mRNA concentrations of all measured mediators except IL‐10, IL‐1β and MCP‐1/2, whereas only CXCL8 was increased (P<0.05) in DEV NON‐RX. Within the OG1 group, CRYO limbs (compared with NON‐RX) had decreased (P<0.05) mRNA concentrations of the majority of measured inflammatory mediators (no change in MCP‐1 and IL‐10). Within the DEV group, mRNA concentrations of CXCL‐1, ICAM‐1, IL‐1β, CXCL8 and MCP‐2 were decreased (P<0.05) and the anti‐inflammatory cytokine IL‐10 was increased (compared with NON‐RX limbs; P<0.05). Conclusions: Digital hypothermia effectively blocked early lamellar inflammatory events likely to play an important role in lamellar injury including the expression of chemokines, proinflammatory cytokines, COX‐2 and endothelial adhesion molecules. Potential relevance: This study demonstrates a potential mechanism by which hypothermia reduces the severity of acute laminitis, and may help identify molecular targets for future laminitis intervention. 相似文献
10.
Crawford C Sepulveda MF Elliott J Harris PA Bailey SR 《Journal of animal science》2007,85(11):2949-2958
Pasture-induced laminitis in the horse is associated with the overconsumption of fermentable carbohydrate, in the form of simple sugars, fructans, or starch. The fermentation of carbohydrate in the cecum and large intestine results in the production of lactic acid and other toxins or "laminitis trigger factors." Vasoactive amines have been suggested as possible initiating factors. The aim of this study was to feed a commercially available form of fructan carbohydrate (inulin, 3 g/kg of BW per day) to normal ponies and to ponies predisposed to laminitis, to mimic a change from a basal hay diet to lush spring-summer pasture. Five normal and 6 laminitis-prone, native-breed ponies were acclimated to a basal hay diet before the inclusion of inulin and chopped dried grass. Blood samples, fecal samples, and foot temperature measurements were taken throughout the study. Amines were measured in the feces and plasma by HPLC and liquid chromatography-mass spectrometry, respectively. The pH of the fecal samples decreased from 6.89 +/- 0.11 on the hay diet to a minimum of 6.18 +/- 0.11 with the addition of inulin (P <0.05). An increase was observed in the fecal concentrations of a number of amines, including tryptamine (2.5-fold increase, P <0.05) and tyramine (2-fold increase, P <0.05). No changes were noted in plasma amine concentrations or plasma D- or L-lactate, indicating that there may be a threshold of hindgut pH change before mucosal damage can result in the release of these factors into the circulation. No differences in pH or any of the measured compounds were observed between the group of normal ponies and those predisposed to laminitis. This indicates that differences in the intestinal microflora do not account for this predisposition. However, the results from this study indicate that moderate increases in dietary fructan carbohydrate can produce increases in bacterial fermentation products and other compounds in the large intestine, which may be relevant to the pathogenesis of acute laminitis in ponies on pasture. 相似文献
11.
12.
Reasons for performing study: Insulin resistance (IR) is a risk factor for pasture‐associated laminitis in equids and alimentary carbohydrate overload may trigger laminitis. Whether glucose metabolism responses to carbohydrate overload are more pronounced in insulin‐resistant horses requires further study. Hypothesis: Horses pretreated with endotoxin to alter insulin sensitivity differ significantly in their glucose and insulin responses to carbohydrate overload. Methods: Horses (n = 24) were divided into 3 groups. A lipopolysaccharide (LPS; n = 8) group that received endotoxin as an 8 h 7.5 ng/kg bwt/h i.v. continuous rate infusion, an oligofructose (OF; n = 8) group that received an infusion of saline followed by 5 g/kg bwt OF via nasogastric intubation, and a LPS/OF (n = 8) group that received LPS followed 16 h later by OF. Glucose and insulin dynamics were evaluated at ‐24 h and 48 h using the frequently sampled i.v. glucose tolerance test and minimal model analysis. Physical examinations and haematology were performed and the severity of laminitis assessed. Results: Horses receiving LPS developed leucopenia and both LPS and OF induced clinical signs consistent with systemic inflammation. Insulin sensitivity significantly decreased (P<0.001) over time, but responses did not differ significantly among groups. Time (P<0.001) and treatment × time (P = 0.038) effects were detected for the acute insulin response to glucose, with mean values significantly increasing in LPS and LPS/OF groups, but not the OF group. Five horses in the LPS/OF group developed clinical laminitis compared with 0 and 2 horses in the LPS and OF groups, respectively. Conclusions: Endotoxaemia and carbohydrate overload reduce insulin sensitivity in horses. Endotoxin pretreatment does not affect the alterations in glucose metabolism induced by carbohydrate overload. Potential relevance: Insulin sensitivity decreases after carbohydrate overload in horses, which may be relevant to the development of pasture‐associated laminitis. 相似文献
13.
Hanne Christine Bertram Bent Ole Petersen Jens ? Duus Mogens Larsen Birgitte-Marie L Raun Niels Bastian Kristensen 《Acta veterinaria Scandinavica》2009,51(1):25
Background
It is unknown which metabolites are responsible for propylene glycol (PG)-induced toxicosis, and a better understanding of the underlying mechanisms explaining incidences of abnormal behaviour of dairy cows fed PG is therefore needed.Methods
The study included three cows of which one developed PG toxicosis. In order to investigate how the metabolism of PG differed in the cow developing toxicosis, proton nuclear magnetic resonance (NMR) spectroscopy was applied on ruminal fluids and blood plasma samples obtained before and after feeding with PG.Results
PG toxicosis was characterized by dyspnea and ruminal atony upon intake of concentrate containing PG. The oxygen saturation of arterial blood haemoglobin and the oxygen pressure in arterial blood decreased along with the appearance of the clinical symptoms. NMR revealed differences in plasma and ruminal content of several metabolites between the cow responding abnormally to PG and the two control cows.Conclusion
It is concluded that PG-toxicosis is likely caused by pulmonary vasoconstriction, but no unusual metabolites directly related to induction of this condition could be detected in the plasma or the ruminal fluid. 相似文献14.
15.
REASONS FOR PERFORMING STUDY: The pathology of equine laminitis has been well-documented 48 h after dosing with oligofructose when clinical lameness and lamellar disintegration is well advanced. Further analysis of the earliest lesions, by collecting lamellar samples at the first sign of foot lameness after oligofructose dosing is required in order to increase understanding of the disease. OBJECTIVES: To investigate lamellar epidermal hemidesmosome damage and basement membrane dysadhesion by transmission electron microscopy (TEM). METHODS: Eight clinically normal, mature Standardbred horses were divided randomly into 2 groups of 4. The treatment group were dosed with oligofructose (10 g/kg bwt) and subjected to euthanasia when shifting weight from one foot to other commenced and at the first sign of lameness during walking and turning. This occurred at 24 h in 3 horses and 30 h in one. The sham treatment control group were dosed with water and subjected to euthanasia after 48 h. Lamellar tissues of the front feet were harvested and processed for ultrastructural study using TEM. RESULTS: Examination by TEM showed excessive waviness of the basement membrane zone and pointed tips of some secondary epidermal lamellae, an ultrastructural lesion typical of laminitis. The average number of hemidesmosomes/microm of basement membrane was decreased and their distance from the centre of the lamina densa of the basement membrane was increased. CONCLUSIONS: Laminitis lesions are detectable 24 h after oligofructose administration. POTENTIAL RELEVANCE: Hindgut events occurring in the first 24 h after dosing have begun the destruction of the hoof lamellar interface. Prevention and treatment strategies should precede lameness if they are to be efficacious. 相似文献
16.
S R van Amstel J K Shearer 《Veterinary Clinics of North America: Food Animal Practice》2001,17(1):73-91, vi
The normal development of the horn capsule (epidermis), with its dermal support (corium), is described. Abnormalities of horn growth may be caused by changes in blood flow (laminitis), the biomechanics of weight bearing, heritable developmental conditions, and other changes of unknown cause. 相似文献
17.
REASONS FOR PERFORMING STUDY: The key lesion of laminitis is separation at the hoof lamellar dermal-epidermal interface. For this to happen the structural and adhesion proteins of the basement membrane zone must be altered. Which proteins and how damage to them leads to the lamellar separation of laminitis is unknown. OBJECTIVES: To investigate lamellar hemidesmosome and cytoskeleton damage and basement membrane dysadhesion using light microscopy (LM) and immunofluorescence microscopy (IFM). METHODS: Cryostat sections of lamellar tissues from 2 control and 6 Standardbred horses with oligofructose induced laminitis were studied using LM and IFM. Plectin, integrin alpha6 and BP230 antibody was used to label hemidesmosome intracellular plaque proteins and anti-BP180 and anti-laminin 5 (L5) was used to label anchoring filament (AF) proteins. Cytoskeleton intermediate filaments were labelled using anti-cytokeratin 14. The primary antibodies of selected sections were double labelled to show protein co-localisation. RESULTS: Laminitis caused reduction of transmembrane integrin alpha6, the AF proteins BP180 and L5, and failure of co-localisation of BP180 and L5. Proteins of the inner hemidesmosomal plaque, plectin and BP230, were unaffected. CONCLUSIONS: Loss of co-localisation of L5 and BP180 suggests that, during the acute phase of laminitis, L5 is cleaved and therefore, the AFs connecting the epidermis to the dermis, fail. Without a full complement of AFs separation at the lamellar dermo-epidermal junction occurs. POTENTIAL RELEVANCE: Suppressing or inhibiting metalloproteinase activity may prevent L5 cleavage and therefore the lamellar dermo-epidermal separation of laminitis. 相似文献
18.
REASONS FOR PERFORMING STUDY: The role of glucocorticoids (GCs) in the pathogenesis of laminitis is incompletely understood. Local tissue activity of GC is regulated by the steroid converting enzyme, 11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD-1). Changes in integumentary (skin and hoof lamellar) 11beta-HSD activity occurring during laminitis could affect the extent to which GCs are involved in its development. HYPOTHESIS: That changes in integumentary 11beta-HSD-1 activity associated with the laminitic condition would lead to elevated local tissue levels of GCs, which could subsequently contribute, through paracrine and autocrine mechanisms, to the further development of laminitis; and that similar changes in 11beta-HSD-1 activity would be evident in both skin and hoof lamellar tissue. METHODS: Activity of 11beta-HSD-1 was determined in skin and hoof lamellar tissue specimens obtained from normal and laminitic horses using a radiometric assay. Skin samples were obtained from 10 normal horses and from 10 horses before and after induction of acute laminitis following administration of starch via nasogastric tube. Hoof lamellar samples were obtained from 10 normal horses, 10 horses following induction of acute laminitis and 4 chronically-foundered horses. Bidirectional 11beta-HSD-1 activity was measured in both skin and lamellar tissues. RESULTS: 11-ketoreductase activity exceeded 11beta-dehydrogenase activity in both skin and lamellar tissues. Cutaneous activity was higher than lamellar 11beta-HSD-1 activity in all groups. Both ketoreductase and dehydrogenase activity increased in skin and lamellae following experimental induction of acute laminitis, but the increase in ketoreductase activity was substantially greater than that for dehydrogenase in the lamellae. Induction of acute laminitis was attended by increases of 227 and 220% in cutaneous dehydrogenase and ketoreductase activity, respectively, and 173 and 398% in lamellar dehydrogenase and ketoreductase activity, respectively (P<0.05). CONCLUSIONS: The 11-ketoreductase moiety of 11beta-HSD-1 plays a role in equine skin and hoof lamellae regarding the regulation of local glucocorticoid activity. Increased 11-ketoreductase activity will lead to increased local tissue GC activity by virtue of conversion of cortisone to cortisol. POTENTIAL RELEVANCE: The laminitic condition is attended by integumentary biochemical changes that enhance the local concentration of cortisol, especially in the hoof lamellar interface. Through multiple and diverse actions, increased local GC activity contributes to the pathogenesis and morbidity associated with laminitis. Pharmacological manipulation of 11beta-HSD-1 deserves further investigation regarding the prevention and treatment of laminitis. 相似文献
19.
With the increasing number of studies being published on the different experimental models used to induce and study acute laminitis, the pathophysiological events associated with these various models (i.e. starch overload, oligofructose overload, black walnut extract and hyperinsulinaemia) can be compared more realistically. Within this review, the mechanisms for metabolic vs. inflammatory laminitis are discussed, and the question of how pasture laminitis may fit into any of the proposed mechanisms is addressed. 相似文献
20.
REASONS FOR PERFORMING STUDY: Light microscopical studies show that the key lesion of laminitis is separation at the hoof lamellar dermal-epidermal interface. More precise knowledge of the damage occurring in the lamellar basement membrane zone may result if laminitis affected tissue is examined with the transmission electron microscope. This could lead to better understanding of the pathogenesis of lesions and the means of treatment or prevention. OBJECTIVES: To investigate the ultrastructure of acute laminitis as disease of greater severity is induced by increasing oligofructose (OF) dosage. METHODS: Three pairs of normal horses, dosed with OF at 7.5, 10 and 12.5 g/kg bwt via nasogastric intubation, developed laminitis 48 h later. Following euthanasia, their forefeet were processed for transmission electron microscopy. Lamellar basal cell hemidesmosome (HD) numbers and the distance between the basal cell plasmalemma and the lamina densa of the basement membrane were estimated and compared to control tissue. RESULTS: Increasing OF dosage caused greater HD loss and more severe laminitis. The characteristic separation of the basement membrane, cytoskeleton failure and rounded basal cell nuclei results from combined HD dysassembly and anchoring filament failure. CONCLUSIONS: Without properly assembled HDs, dysadhesion between the lamina densa of the basement membrane (BM) and epidermal basal cells occurs, emphasising the fundamental importance of HDs in maintaining attachment at the lamellar interface. Medical conditions that trigger lamellar matrix metalloproteinase (MMP) activation and/or compromise entry of glucose into lamellar basal cells appear to promote loss and failure of HDs and, therefore, laminitis development. POTENTIAL RELEVANCE: A correlation between lameness severity and escalating loss of lamellar HDs now exists. Therapy aimed at protecting the lamellar environment from haematogenous delivery of MMP activators or from glucose deprivation may control laminitis development. 相似文献