Oxidative species increase arginase activity in endothelial cells through the RhoA/Rho kinase pathway.

Background And Purpose: NO produced by endothelial NOS is needed for normal vascular function. During diabetes, aging and hypertension, elevated levels of arginase can compete with NOS for available l-arginine, reducing NO and increasing superoxide (O(2) (.-)) production via NOS uncoupling.

Hyperoxia therapy of pre-proliferative ischemic retinopathy in a mouse model.

Purpose: To investigate the therapeutic use and mechanisms of action of normobaric hyperoxia to promote revascularization and to prevent neovascularization in a mouse model of oxygen-induced ischemic retinopathy.

Methods: Hyperoxia treatment (HT, 40%-75% oxygen) was initiated on postnatal day (P) 14 during the pre-proliferative phase of ischemic retinopathy. Immunohistochemistry, ELISA, and quantitative PCR were used to assess effects on retinal vascular repair and pathologic angiogenesis in relation to glial cell injury, VEGF protein, and mRNA levels of key mediators of pathologic angiogenesis.

Increased folding and channel activity of a rare cystic fibrosis mutant with CFTR modulators.

Cystic fibrosis (CF) is a lethal recessive genetic disease caused by mutations in the CFTR gene. The gene product is a PKA-regulated anion channel that is important for fluid and electrolyte transport in the epithelia of lung, gut, and ducts of the pancreas and sweat glands. The most common CFTR mutation, ΔF508, causes a severe, but correctable, folding defect and gating abnormality, resulting in negligible CFTR function and disease.

Anti-inflammatory therapy for diabetic retinopathy.

Diabetic retinopathy (DR) is one of the most common complications of diabetes. This devastating disease is a leading cause of blindness in people of working age in industrialized countries and affects the daily lives of millions of people. Despite tight glycemic control, blood pressure control and lipid-lowering therapy, the number of DR patients keeps growing and therapeutic approaches are limited.

A(₂A) adenosine receptor (A(₂A)AR) as a therapeutic target in diabetic retinopathy.

In diabetic retinopathy (DR), abnormalities in vascular and neuronal function are closely related to the local production of inflammatory mediators whose potential source is microglia. A(₂A) adenosine receptor (A(₂A)AR) has been shown to possess anti-inflammatory properties that have not been studied in DR. Here, we evaluate the role of A(₂A)AR and its underlying signaling in retinal complications associated with diabetes.

Reactive oxygen species-dependent RhoA activation mediates collagen synthesis in hyperoxic lung fibrosis.

Lung fibrosis is an ultimate consequence of pulmonary oxygen toxicity in human and animal models. Excessive production and deposition of extracellular matrix proteins, e.g.

The role of N-methyl-D-aspartate receptor activation in homocysteine-induced death of retinal ganglion cells.

Purpose: Elevated plasma homocysteine has been implicated in glaucoma, a vision disorder characterized by retinal ganglion cell death. The toxic potential of homocysteine to ganglion cells is known, but the mechanisms are not clear. A mechanism of homocysteine-induced death of cerebral neurons is via N-methyl-D-aspartate (NMDA) receptor overstimulation, leading to excess calcium influx and oxidative stress.

Angiotensin II-induced vascular endothelial dysfunction through RhoA/Rho kinase/p38 mitogen-activated protein kinase/arginase pathway.

Enhanced vascular arginase activity impairs endothelium-dependent vasorelaxation by decreasing l-arginine availability to endothelial nitric oxide (NO) synthase, thereby reducing NO production. Elevated angiotensin II (ANG II) is a key component of endothelial dysfunction in many cardiovascular diseases and has been linked to elevated arginase activity. We determined signaling mechanisms by which ANG II increases endothelial arginase function.

The role of RhoA/Rho kinase pathway in endothelial dysfunction.

Endothelial dysfunction is a key event in the development of vascular disease, and it precedes clinically obvious vascular pathology. Abnormal activation of the RhoA/Rho kinase (ROCK) pathway has been found to elevate vascular tone through unbalancing the production of vasodilating and vasoconstricting substances. Inhibition of the RhoA/ROCK pathway can prevent endothelial dysfunction in a variety of pathological conditions.

Ontogeny of tetrodotoxin levels in blue-ringed octopuses: maternal investment and apparent independent production in offspring of Hapalochlaena lunulata.

Many organisms provision offspring with antipredator chemicals. Adult blue-ringed octopuses (Hapalochlaena spp.) harbor tetrodotoxin (TTX), which may be produced by symbiotic bacteria.

Assessment of length distributions between non-coding and coding sequences amongst two model organisms.

The availability of genomic DNA and cDNA sequence data has escalated the data mining and genomics era. We aim to investigate the length distributions of the non-coding and coding regions of protein genes of two model organisms, Arabidopsis thaliana and Drosophila melanogaster. A non-linear functional relationship model was applied and strong correlation was found between the Coding Sequence (CDS) and non-coding sequence regions, conditional on the 5' UTR data.

Genetic and biochemical analysis of base excision repair complexes participating in radiation-induced ROS damage repair.

This work is part of the joint research project 'radiation-induced DNA damage' of the KVSF, a BMBF Initiative (maintenance of radiation biology expertise in Germany). The focus of the research is the mechanism of DNA repair, specifically damage repair aspects arising from radiation-induced reactive oxygen species production. The authors will systematically look at potential accessory proteins associated with primarily base excision repair using molecular and biochemical methods.

Arginase II deletion increases corpora cavernosa relaxation in diabetic mice.

Introduction: Diabetes-induced erectile dysfunction involves elevated arginase (Arg) activity and expression. Because nitric oxide (NO) synthase and Arg share and compete for their substrate L-arginine, NO production is likely linked to regulation of Arg. Arg is highly expressed and implicated in erectile dysfunction.

Peroxynitrite mediates diabetes-induced endothelial dysfunction: possible role of Rho kinase activation.

Endothelial dysfunction is characterized by reduced bioavailability of NO due to its inactivation to form peroxynitrite or reduced expression of eNOS. Here, we examine the causal role of peroxynitrite in mediating diabetes-induced endothelial dysfunction. Diabetes was induced by STZ-injection, and rats received the peroxynitrite decomposition catalyst (FeTTPs, 15 mg/Kg/day) for 4 weeks.

Cannabidiol As a Putative Novel Therapy for Diabetic Retinopathy: A Postulated Mechanism of Action as an Entry Point for Biomarker-Guided Clinical Development.

Diabetic retinopathy is a leading cause of blindness in the Western world. However, treatment options for diabetic retinopathy are limited and display poor efficacy with marked patient-to-patient variation in therapeutic outcomes. Discovery of new molecular entities acting on mechanistically novel biological pathways remains as one of the key research priorities in diabetic retinopathy.

Acquired toxoplasmosis after orthotopic heart transplantation in a sulfonamide-allergic patient.

We report the case of a young adult with a history of an allergic reaction to a sulfonamide antibiotic who developed toxoplasmosis after his second orthotopic heart transplant. As a result of this drug allergy, the patient did not receive prophylaxis with trimethoprim and sulfamethoxazole. He was successfully treated with clindamycin, pyrimethamine, and folic acid.

Evolution of anatomical and physiological specialization in the compound eyes of stomatopod crustaceans.

Stomatopod crustaceans have complex and diverse visual systems. Among their many unique features are a specialized ommatidial region (the midband) that enables the eye to have multiple overlapping visual fields, as well as sets of spectral filters that are intercalated at two levels between tiers of photoreceptors involved in polychromatic color vision. Although the physiology and visual function of stomatopod eyes have been studied for many years, how these unique visual features originated and diversified is still an open question.

Novel mechanisms of endothelial dysfunction in diabetes.

Diabetes mellitus is a major risk factor for cardiovascular morbidity and mortality. This condition increases the risk of developing coronary, cerebrovascular, and peripheral arterial disease fourfold. Endothelial dysfunction is a major contributor to the pathogenesis of vascular disease in diabetes mellitus patients and has recently received increased attention.

Long radiology workdays reduce detection and accommodation accuracy.

Purpose: The aim of this study was to measure the diagnostic accuracy of fracture detection, visual accommodation, reading time, and subjective ratings of fatigue and visual strain before and after a day of clinical reading.

Methods: Forty attending radiologists and radiology residents viewed 60 deidentified, HIPAA-compliant bone examinations, half with fractures, once before any clinical reading (early) and once after a day of clinical reading (late). Reading time was recorded.

p38 Mitogen-activated protein kinase (MAPK) increases arginase activity and contributes to endothelial dysfunction in corpora cavernosa from angiotensin-II-treated mice.

Introduction: Angiotensin II (AngII) activates p38 mitogen-activated protein kinase (MAPK) and elevates arginase activity in endothelial cells. Upregulation of arginase activity has been implicated in endothelial dysfunction by reducing nitric oxide (NO) bioavailability. However, signaling pathways activated by AngII in the penis are largely unknown.

Notch3 is critical for proper angiogenesis and mural cell investment.

Rationale: The heterotypic interactions of endothelial cells and mural cells (smooth muscle cells or pericytes) are crucial for assembly, maturation, and subsequent function of blood vessels. Yet, the molecular mechanisms underlying their association have not been fully defined.

Objective: Our previous in vitro studies indicated that Notch3, which is expressed in mural cells, mediates these cell-cell interactions.

Acute activation of eNOS by statins involves scavenger receptor-B1, G protein subunit Gi, phospholipase C and calcium influx.

Background And Purpose: Statins (HMG CoA reductase inhibitors) have beneficial effects independent of reducing cholesterol synthesis and this includes their ability to acutely activate endothelial nitric oxide synthase (eNOS). The mechanism by which this occurs is largely unknown and thus we characterized the pathways by which statins activate NOS, including involvement of scavenger receptor-B1 (SR-B1), which is expressed in endothelial cells and maintains cholesterol concentrations.

Experimental Approach: Nitric oxide production was monitored in bovine aortic endothelial cells (BAECs) exposed to lovastatin (LOV) or pravastatin (PRA) for 10-20 min, alone or following pre-exposure to the end product of HMG-CoA reductase (mevalonate), G protein inhibitors (pertussis/cholera toxins), phospholipase C (PLC) inhibitor (U-73122), or intracellular and extracellular calcium chelators - BAPTA-AM and EGTA (respectively), or a function blocking antibody to SR-B1.

Building self-assembled molecular layers with axially substituted titanium phthalocyanines.

Adsorption on graphite (HOPG) by titanium phthalocyanine axially bonded to a catechol ligand (TiPcat), titanylphthalocyanine (TiOPc), and 1:1 mixtures of these are studied at the HOPG-octylbenzene interface. The surface structures of a two-component bilayer, and of the individual monolayers of TiOPc and TiPcat, were determined by scanning tunneling microscopy (STM). TiPcat self-segregates onto a monolayer of TiOPc when an equal molar mixture is used.