5-Lipoxygenase, but not 12/15-lipoxygenase, contributes to degeneration of retinal capillaries in a mouse model of diabetic retinopathy.

Objective: Lipoxygenases are regulators of chronic inflammation and oxidative stress generation. We evaluated the role of 5- and 12-lipoxygenases in the development of diabetic retinopathy.

Research Design And Methods: Wild-type mice, 5-lipoxygenase-deficient mice, and 12/15-lipoxygenase-deficient mice were assessed 1) after 9 months of diabetes for retinal histopathology and leukotriene receptor expression and 2) after 3 months of diabetes for leukostasis and retinal superoxide generation.

Contributions of inflammatory processes to the development of the early stages of diabetic retinopathy.

Diabetes causes metabolic and physiologic abnormalities in the retina, and these changes suggest a role for inflammation in the development of diabetic retinopathy. These changes include upregulation of iNOS, COX-2, ICAM-1, caspase 1, VEGF, and NF-kappaB, increased production of nitric oxide, prostaglandin E2, IL-1beta, and cytokines, as well as increased permeability and leukostasis. Using selective pharmacologic inhibitors or genetically modified animals, an increasing number of therapeutic approaches have been identified that significantly inhibit development of at least the early stages of diabetic retinopathy, especially occlusion and degeneration of retinal capillaries.

Targets of tyrosine nitration in diabetic rat retina.

Diabetic retinopathy, a retinal vascular disease, is inhibited in animals treated with aminoguanidine, an inhibitor of inducible nitric-oxide synthase. This treatment also reduces retinal protein nitration, which is greater in diabetic rat retina than nondiabetic retina. As an approach to understanding the molecular mechanisms of diabetic retinopathy, we sought the identity of nitrotyrosine-containing proteins in retina from streptozotocin-induced diabetic rats and in a rat retinal Müller cell line grown in high glucose (25 mM).

Sensitivity-enhanced IPAP-SOFAST-HMQC for fast-pulsing 2D NMR with reduced radiofrequency load.

The SOFAST-HMQC experiment [P. Schanda, B. Brutscher, Very fast two-dimensional NMR spectroscopy for real-time investigation of dynamic events in proteins on the time scale of seconds, J.

Long-term, topical insulin administration increases the severity of retinal vascular pathology in streptozotocin-induced diabetic rats.

Background: We previously reported that insulin accumulated in the retina of diabetic rats after topical insulin eye drop treatment. In light of insulin's reported benefits to the retina, we hypothesized that the delivery of insulin to the retina by eye drop application might be efficacious in preventing diabetic retinopathy.

Methods: We applied daily, uni-ocular porcine insulin drops (0.

Captopril inhibits capillary degeneration in the early stages of diabetic retinopathy.

Purpose: This study was conducted to examine the effect of angiotensin-converting enzyme (ACE) inhibitors on the development of early stages of diabetic retinopathy.

Methods: Rats were made diabetic by injection of streptozotocin and treated with the ACE inhibitor captopril and the AT1 antagonist losartan. The extent of capillary degeneration and leukostasis in the retina were determined.

[Complications after refractive surgery abroad].

Background: In this article a retrospective analysis of patients presenting at a German university following refractive surgery abroad is presented.

Patients And Methods: A total of 20 cases of patients who had undergone treatment between 1998 and 2006 in China (1 case), Greece (1 case), Iran (1 case), Russia (2 cases), Switzerland (1 case), Slovakia (1 case), Spain (2 cases), South Africa (3 cases), Turkey (6 cases) and the USA (2 cases) were analyzed retrospectively.

Results: The following complications were observed: epithelial ingrowth into the interface with or without melting of the flap (6 cases), corneal ectasia (2 cases), dislocation of a phakic posterior chamber intraocular lens and prolapse into the anterior chamber with endothelial cell loss (1 case), secondary increase of intraocular pressure following implantation of a phakic intraocular lens (1 case), flap-related complications following laser-in-situ keratomileusis (LASIK) (2 cases), keratitis (1 case), dislocation of the complete flap (1 case), diffuse lamellar keratitis (DLK) grade IV (1 case), hyperopia as a consequence of radial keratotomy (1 case), and under correction/over correction and poor optical quality following laser epithelial keratomileusis (LASEK) and LASIK for high myopia (5 cases) with possible early corneal ectasia.

Oxidative damage in the retinal mitochondria of diabetic mice: possible protection by superoxide dismutase.

Purpose: Superoxide levels are elevated in the retina in patients with diabetes, and cytochrome c is released from the mitochondria. The purpose of this study was to elucidate the mechanism involved in the oxidative damage of retinal mitochondria in diabetes and to determine whether mitochondrial superoxide dismutase (MnSOD) provides protection.

Methods: Effects of diabetes were investigated on superoxide and GSH levels, electron transport complexes I and III, and membrane permeability in the isolated mitochondria prepared from the retinas of streptozotocin diabetic mice.

Pharmacokinetic comparisons of tail-bleeding with cannula- or retro-orbital bleeding techniques in rats using six marketed drugs.

Introduction: The evaluation of drug disposition properties of chemical entities in drug discovery research typically involves the conduct of pharmacokinetic studies in rodents that requires blood sampling over several time points, preferably without disrupting the physiological status of the animals. Several blood withdrawal methods have been employed throughout the industry, yet these methods have not been comprehensively evaluated with regard to their effects on pharmacokinetic profiles of the drug investigated to recommend best practices.

Methods: In this paper, the pharmacokinetics of six marketed drugs from four distinct therapeutic classes were compared using tail-vein, femoral-artery cannula-, and retro-orbital sinus bleeding techniques.

Critical role of inducible nitric oxide synthase in degeneration of retinal capillaries in mice with streptozotocin-induced diabetes.

Aims/hypothesis: Diabetes results in the upregulation of the production of several components of the inflammatory response in the retina, including inducible nitric oxide synthase (iNOS). The aim of this study was to investigate the role of iNOS in the pathogenesis of the early stages of diabetic retinopathy using iNOS-deficient mice (iNos (-/-)).

Materials And Methods: iNos (-/-) mice and wild-type (WT; C57BL/6J) mice were made diabetic with streptozotocin or kept as non-diabetic controls.

6-Fluoro-6-deoxy-D-glucose as a tracer of glucose transport.

Glucose transport rates are estimated noninvasively in physiological and pathological states by kinetic imaging using PET. The glucose analog most often used is (18)F-labeled 2FDG. Compared with glucose, 2FDG is poorly transported by intestine and kidney.

Ischemic vascular damage can be repaired by healthy, but not diabetic, endothelial progenitor cells.

Endothelial precursor cells (EPCs) play a key role in vascular repair and maintenance, and their function is impeded in diabetes. We previously demonstrated that EPCs isolated from diabetic patients have a profound inability to migrate in vitro. We asked whether EPCs from normal individuals are better able to repopulate degenerate (acellular) retinal capillaries in chronic (diabetes) and acute (ischemia/reperfusion [I/R] injury and neonatal oxygen-induced retinopathy [OIR]) animal models of ocular vascular damage.

Glutaredoxin regulates nuclear factor kappa-B and intercellular adhesion molecule in Müller cells: model of diabetic retinopathy.

Reversible S-glutathionylation of proteins is a focal point of redox signaling and cellular defense against oxidative stress. This post-translational modification alters protein function, and its reversal (deglutathionylation) is catalyzed specifically and efficiently by glutaredoxin (GRx, thioltransferase), a thioldisulfide oxidoreductase. We hypothesized that changes in glutaredoxin might be important in the development of diabetic retinopathy, a condition characterized by oxidative stress.

Topical administration of nepafenac inhibits diabetes-induced retinal microvascular disease and underlying abnormalities of retinal metabolism and physiology.

Pharmacologic treatment of diabetic retinopathy via eyedrops could have advantages but has not been successful to date. We explored the effect of topical Nepafenac, an anti-inflammatory drug known to reach the retina when administered via eyedrops, on the development of early stages of diabetic retinopathy and on metabolic and physiologic abnormalities that contribute to the retinal disease. Streptozotocin-induced diabetic rats were assigned to three groups (0.

Salicylate-based anti-inflammatory drugs inhibit the early lesion of diabetic retinopathy.

It has been previously reported that aspirin inhibited the development of diabetic retinopathy in diabetic animals, raising the possibility that anti-inflammatory drugs may have beneficial effects on diabetic retinopathy. To further explore this, we compared effects of oral consumption of three different salicylate-based drugs (aspirin, sodium salicylate, and sulfasalazine) on the development of early stages of diabetic retinopathy in rats. These three drugs differ in their ability to inhibit cyclooxygenase but share an ability to inhibit nuclear factor-kappaB (NF-kappaB).

Intraindividual comparison of human radial and internal thoracic arteries in vitro and the effect of preoperative calcium blocker therapy.

The patency rate of radial artery (RA) conduits is considerably lower than that of internal thoracic artery (ITA) grafts and the evidence suggests that this is due to a clinically suspected higher incidence of vasospasm. The aim of this study was, therefore, to compare intraindividually the pharmacological reactivity of RA with that of ITA. Both RA and ITA were taken from the same patients and investigated in parallel.

Retinal ischemia and reperfusion causes capillary degeneration: similarities to diabetes.

Purpose: Retinal neurons and vasculature interact with each other under normal conditions, and occlusion of the retinal vasculature can result in damage to retinal neurons. Whether damage to the neural retina will damage the vasculature, however, is less clear. This study was conducted to explore the relationship between vascular and nonvascular cells of the retina.

Tetra-kis(triphenyl-arsine)copper(I) hexa-fluoridophosphate.

In the crystal structure of the title compound, [Cu(C(18)H(15)As)(4)]PF(6), the Cu atom is coordinated by four As atoms of triphenyl-arsine ligands in a tetra-hedral geometry. The complex cation is located on a crystallographic threefold axis. Both PF(6) (-) anions are located on special positions of site symmetry .

Reduction of diabetes-induced oxidative stress, fibrotic cytokine expression, and renal dysfunction in protein kinase Cbeta-null mice.

Diabetes induces the activation of several protein kinase C (PKC) isoforms in the renal glomeruli. We used PKC-beta(-/-) mice to examine the action of PKC-beta isoforms in diabetes-induced oxidative stress and renal injury at 8 and 24 weeks of disease. Diabetes increased PKC activity in renal cortex of wild-type mice and was significantly reduced (<50% of wild-type) in diabetic PKC-beta(-/-) mice.

Corneal ulceration associated with naturally occurring canine herpesvirus-1 infection in two adult dogs.

Case Description: An 8-year-old Labrador Retriever with diabetes mellitus in which bilateral phacoemulsification had been performed 3 weeks earlier was evaluated for acute onset of blepharospasm, and a 7-year-old Miniature Schnauzer with chronic immune-mediated thrombocytopenia was reevaluated for keratoconjunctivitis sicca that had been diagnosed 4 weeks earlier.

Clinical Findings: Dendritic corneal ulcerations were detected in both dogs. Canine herpesvirus-1 (CHV-1) was isolated from corneal swab specimens obtained during the initial evaluation of each dog and during recheck examinations performed until the ulcerations were healed.

[Treatment of infected total knee arthroplasty. When does implant salvage make sense?].

Infection of a total knee arthroplasty can be classified as acute, chronic and haematogenic with and without implant loosening. A differentiated treatment concept for all types of infection is necessary. Furthermore, specific treatment has to be initiated early, as any delay is associated with a worsening of the prognosis.

Association between endothelin-1 and collagen deposition in db/db diabetic mouse kidneys.

Endothelin-1 has been implicated in diabetic kidney injury, but there are few firm data establishing the temporal and spatial expression of kidney endothelin-1 in diabetes. We performed an immunohistochemical and histopathological analysis to determine endothelin-1 peptide expression in the kidneys of diabetic db/db mice and non-diabetic db/m controls. Diabetic mice were studied at 8 weeks, before histological damage is evident, and again at 16 weeks, when significant glomerular injury has occurred.

Vascular damage in a mouse model of diabetic retinopathy: relation to neuronal and glial changes.

Purpose: Lack of information about the development of diabetic retinopathy in mice has greatly hindered the use of genetic mouse models for the study of disease mechanisms and the development of therapeutic strategies. The objective of this study was to characterize the occurrence and pathologic progression of diabetic retinopathy in C57Bl/6J mice.

Methods: Diabetes was induced with five consecutive injections of streptozotocin (STZ).

Vertical position of the patella in the stifle joint of clinically normal large-breed dogs.

Objective: To define the vertical position of the patella in clinically normal large-breed dogs.

Sample Population: Cadavers of 13 clinically normal large-breed dog.

Procedure: Both hind limbs were harvested with intact stifle joints and mounted on a positioning device that allowed full range of motion of the stifle joint.

The Ins2Akita mouse as a model of early retinal complications in diabetes.

Purpose: This study tested the Ins2(Akita) mouse as an animal model of retinal complications in diabetes. The Ins2(Akita) mutation results in a single amino acid substitution in the insulin 2 gene that causes misfolding of the insulin protein. The mutation arose and is maintained on the C57BL/6J background.