Surface quality of human corneal lenticules after femtosecond laser surgery for myopia comparing different laser parameters

Background  

To determine the surface characteristics of human corneal lenticules after femtosecond laser surgery for myopia.     

Hydrogen peroxide is a novel mediator of inflammatory hyperalgesia,acting via transient receptor potential vanilloid 1-dependent and independent mechanisms

Inflammatory diseases associated with pain are often difficult to treat in the clinic due to insufficient understanding of the nociceptive pathways involved. Recently, there has been considerable interest in the role of reactive oxygen species (ROS) in inflammatory disease, but little is known of the role of hydrogen peroxide (H₂O₂) in hyperalgesia. In the present study, intraplantar injection of H₂O₂-induced a significant dose- and time-dependent mechanical and thermal hyperalgesia in the mouse hind paw, with increased c-fos activity observed in the dorsal horn of the spinal cord. H₂O₂ also induced significant nociceptive behavior such as increased paw licking and decreased body liftings. H₂O₂ levels were significantly raised in the carrageenan-induced hind paw inflammation model, showing that this ROS is produced endogenously in a model of inflammation. Moreover, superoxide dismutase and catalase significantly reduced carrageenan-induced mechanical and thermal hyperalgesia, providing evidence of a functionally significant endogenous role. Thermal, but not mechanical, hyperalgesia in response to H₂O₂ (i.pl.) was longer lasting in TRPV1 wild type mice compared to TRPV1 knockouts. It is unlikely that downstream lipid peroxidation was increased by H₂O₂. In conclusion, we demonstrate a notable effect of H₂O₂ in mediating inflammatory hyperalgesia, thus highlighting H₂O₂ removal as a novel therapeutic target for anti-hyperalgesic drugs in the clinic.     

Genetically determined heterogeneity in hemoglobin scavenging and susceptibility to diabetic cardiovascular disease

A major function of haptoglobin (Hp) is to bind hemoglobin (Hb) to form a stable Hp-Hb complex and thereby prevent Hb-induced oxidative tissue damage. Clearance of the Hp-Hb complex can be mediated by the monocyte/macrophage scavenger receptor CD163. We recently demonstrated that diabetic individuals homozygous for the Hp 2 allele (Hp 2-2) were at 500% greater risk of cardiovascular disease (CVD) compared with diabetic individuals homozygous for the Hp 1 allele (Hp 1-1). No differences in risk by Hp type were seen in individuals without diabetes. To understand the relationship between the Hp polymorphism and diabetic CVD, we sought to identify differences in antioxidant and scavenging functions between the Hp types and to determine how these functions were modified in diabetes. The scavenging function of Hp was assessed using rhodamine-tagged and 125I-Hp in cell lines stably transfected with CD163 and in macrophages expressing endogenous CD163. We found that the rate of clearance of Hp 1-1-Hb by CD163 is markedly greater than that of Hp 2-2-Hb. Diabetes is associated with an increase in the nonenzymatic glycosylation of serum proteins, including Hb. The antioxidant function of Hp was assessed with glycosylated and nonglycosylated Hb. We identified a severe impairment in the ability of Hp to prevent oxidation mediated by glycosylated Hb. We propose that the specific interaction between diabetes, CVD, and Hp genotype is the result of the heightened urgency of rapidly clearing glycosylated Hb-Hp complexes from the subendothelial space before they can oxidatively modify low-density lipoprotein to atherogenic oxidized low-density lipoprotein.     

Hypothesis--haptoglobin genotype and diabetic nephropathy

Vascular complications cause serious morbidity in patients with diabetes mellitus. Three such complications are nephropathy, retinopathy and accelerated atherosclerotic cardiovascular disease. There is currently scant evidence of a genetic marker that predicts which patients will have vascular complications. Oxidative stress has an important role in the development of diabetic vascular complications. Haptoglobin (Hp) is a hemoglobin-binding protein that has a major role in protecting against heme-driven oxidative stress. There are two common alleles for Hp (1 and 2) and, therefore, three common Hp genotypes: Hp 1-1, Hp 2-1, and Hp 2-2. The antioxidant protection provided by Hp is genotype-dependent; the protein encoded by Hp 1-1 provides superior antioxidant protection compared with that encoded by Hp 2-2. We have shown that diabetic individuals with Hp 2-2 are more likely to develop nephropathy, retinopathy, and cardiovascular disease than those with the Hp 2-1 or Hp 1-1 genotypes.     

Synthesis of 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic acid derivatives of potential anti-inflammatory activity

A series of 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic acid derivatives 4-10 were synthesized by rearrangement of 4-(3-pyridyl)-hydrazono-2-phenyl-2-oxazolin-5-one 3 in the presence of different nucleophiles to afford derivatives 4, 7, and 8, while hydroxamic acid derivative 6 was prepared from reaction of methyl ester 4 with hydroxylamine hydrochloride. Semicarbazide 9 and thiosemicarbazide 10, derivatives of the 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic acid, were synthesized via hydrazide 8 with potassium cyanate and appropriate isothiocyanate, respectively. The structures of the synthesized compounds were confirmed by elemental analyses, IR, (1)H-NMR, and mass spectra. The results of the anti-inflammatory activity of the synthesized derivatives showed that most of the tested compounds 4-10 showed significant inhibition against carrageenan-induced rat paw edema in albino rats. Derivatives 4 and 8 showed promising results and were found to be equipotent or more potent than Indomethacin and Celecoxib as reference drugs at two dose levels, 5 and 10 mg/kg, and they have no ulcerogenic activity.