A light-driven rhythm in neurotensin-like immunoreactivity in the chicken retina

Purpose: To determine if the pattern of release of neurotensin from the enkephalin-, neurotensin- and somatostatin-like immunoreactive amacrine cells in response to light and dark is the same as that of the enkephalins and somatostatin. Methods/Results: Both the enkephalins and somatostatin are released at high rates in the dark and at lower rates in the light, and these rate changes are reflected in increasing intracellular levels of the peptides in vivo in the light and decreasing levels in the dark The levels of neurotensin-like immunoreactivity show a similar diurnal light-driven and non-circadian rhythm in vivo. Conclusion: This implies that the actual release rates of neurotensin follow the same patterns as those demonstrated in vitro for the enkephalins and somatostatin.     

Macro design morphology of endosseous dental implants

STATEMENT OF PROBLEM: The identification of dental implant bodies in patients without available records is a considerable problem due to increased patient mobility and to the large number of implant systems with different designs. PURPOSE: The purpose of this study was to document the designs of selected implants to help clinicians identify these implants from their radiographic images. MATERIAL AND METHODS: More than 50 implant manufacturers were contacted and asked to provide implants with dimensions as close as possible to 3.75 mm (diameter) x 10 mm (length). Forty-four implants were donated, separated into threaded and non-threaded categories, and further sorted into tapered and non-tapered categories. The implants were examined visually, and features on the entire circumference and length of each implant were recorded and categorized as coronal, midbody, or apical. RESULTS: A series of tables describe the 44 implants according to coronal, midbody, and apical features. CONCLUSION: The results of this project offer dentists basic knowledge of the design of selected dental implants. Such knowledge can aid the radiographic identification of these implants.     

儿童眼结节病1例

结节病是一种罕见的和潜在的致残儿科疾病。此病临床治疗困难,需要长期监测。我们报告了1例9岁的白人女孩的情况,就诊最初表现为双侧慢性前葡萄膜炎、白内障和继发于结节病的青光眼。在过去的2a,患者接受左布诺洛尔滴剂,局部和全身类固醇治疗,随后要求折叠式人工晶状体植入。在白内障手术后的2mo,患者葡萄膜炎以局部类固醇和低剂量甲氨蝶呤一直控制良好。她全血计数和肾功能定期监测,没有甲氨蝶呤不良影响的报告。结节病是一多系统疾病,需要眼科学家,神经学家和儿科医师多学科的投入。内科和外科治疗本病富于挑战。本例强调了低剂量甲氨蝶呤在儿童慢性葡萄膜炎治疗中的安全性和对此病及时治疗以防止显著发病的需要。     

Evaluation Of Alpha 1-Adrenoceptor Antagonist On Diabetes-Induced Changes In Peripheral Nerve Function, Metabolism, And Antioxidative Defense

The role for nerve blood flow (NBF) vs. other factors in motor nerve conduction (MNC) slowing in short-term diabetes was assessed by evaluating alpha(1)-adrenoceptor antagonist prazosin on NBF, MNC, as well as metabolic imbalances and oxidative stress in the neural tissue. Control and diabetic rats were treated with or without prazosin (5 mg.kg (−1).d(−1) for 3 wk). NBF was measured by hydrogen clearance. Both endoneurial vascular conductance and MNC velocity were decreased in diabetic rats vs. controls, and this decrease was prevented by prazosin. Free NAD(+):NADH ratios in mitochondrial cristae, matrix, and cytosol assessed by metabolite indicator method, as well as phosphocreatine levels and phosphocreatine/creatine ratios, were decreased in diabetic rats, and this reduction was ameliorated by prazosin. Neither diabetes-induced accumulation of two major glycation agents, glucose and fructose, as well as sorbitol and total malondialdehyde plus 4-hydroxyalkenals nor depletion of myo-inositol, GSH, and taurine or decrease in (Na/K)-ATP-ase activity were affected by prazosin. In conclusion, decreased NBF, but not metabolic imbalances or oxidative stress in the neural tissue, is a key mechanism of MNC slowing in short-term diabetes. Further experiments are needed to estimate whether preservation of NBF is sufficient for prevention of nerve dysfunction and morphological abnormalities in long-standing diabetes or whether the aforementioned metabolic imbalances closely associated with impaired neurotropism are of greater importance in advanced than in early diabetic neuropathy.     

Biochemical and pharmacological characterization of AZD1981, an orally available selective DP2 antagonist in clinical development for asthma

Background and Purpose

The discovery of DP₂ as a second receptor for PGD₂ has prompted the search for antagonists as potential novel therapies based on the associations between PGD₂ and disease. Here we describe the biochemical and pharmacological properties of 4-(acetylamino)-3-[(4-chlorophenyl)thio]-2-methyl-1H-indole-1-acetic acid (AZD1981), a novel DP₂ receptor antagonist.

Experimental Approach

Binding to DP₂, functional receptor pharmacology and selectivity were studied in both human and animal systems.

Key Results

AZD1981 displaced radio-labelled PGD₂ from human recombinant DP₂ with high potency (pIC₅₀ = 8.4). Binding was reversible, non-competitive and highly selective against a panel of more than 340 other enzymes and receptors, including DP₁ (>1000-fold selective). AZD1981 inhibited DP₂-mediated shape change and CD11b up-regulation in human eosinophils, shape change in basophils and chemotaxis of human eosinophils and Th2 cells with similar potency. AZD1981 exhibited good cross-species binding activity against mouse, rat, guinea pig, rabbit and dog DP₂. Evaluation in mouse, rat or rabbit cell systems was not possible as they did not respond to DP₂ agonists. Agonist responses were seen in guinea pig and dog, and AZD1981 blocked DP₂-mediated eosinophil shape change. Such responses were more robust in the guinea pig, where AZD1981 also blocked DP₂-dependent eosinophil emigration from bone marrow.

Conclusions and Implications

AZD1981 is a DP₂ antagonist that blocks functional responses in eosinophils, Th2 cells and basophils. It exhibited similar potency irrespective of the cell type, DP₂ agonist or species used. This selective orally active agent is currently under clinical evaluation as a potential therapeutic agent in respiratory diseases including asthma.     

Localization of D, dopamine receptors in the chicken retina

Purpose: The localization of dopamine D| receptors (DIR) in the chicken retina was examined using an anti-human DI R. monoclonal antibody and PAP techniques. Results: A clear band of staining was seen in the outer plex-iform layer; as well as cellular staining in the outer-most part of the inner nuclear layer probably in a subset of horizontal cells. Many different amacrine cell bodies were labelled in the inner one-third of the inner nuclear layer. There was also extensive staining in the inner plexiform layer; which showed some striation. Occasional labelled ganglion cells were also detected. Conclusion: Localization of DI-dopamine receptors has     

A fundamental step-transition in retinal function at low light intensities

There appears to be a fundamental step-transition in retinal function at low light intensities, close to the scotopic-mesopic transition. This step-transition is observed for elements of the retinal dark-light switch, which has been described in the chicken retina. Over the same range of light intensities, there is a step-transition in photoreceptor retinomotor movements and in the coupling of horizontal and All amacrine cells, which suggests a switch in retinal circuitry from rod-processing to cone-processing regimes. A similar step-transition in pineal function suggests that the retinal step-transition signals to the central circadian systems. Finally, this step-transition may also inhibit eye growth, and thus be responsible for the reported diurnal rhythm in eye growth. Disturbances to this step-transition may be the initial cause of disordered eye growth in the form-deprivation myopia paradigm.     

Genes harbouring susceptibility SNPs are differentially expressed in the breast cancer subtypes

Recently, genome-wide association studies of breast cancer revealed single nucleotide polymorphisms (SNPs) in five genes with novel association to susceptibility. While there is little doubt that the novel susceptibility markers produced from such highly powered studies are true, the mechanisms by which they cause the susceptibility remain undetermined. We have looked at the expression levels of the identified genes in tumours and found that they are highly significantly differentially expressed between the five established breast cancer subtypes. Also, a significant association between SNPs in these genes and their expression in tumours was seen as well as a significantly different frequency of the SNPs between the subtypes. This suggests that the observed genes are associated with different breast cancer subtypes, and may exert their effect through their expression in the tumours. Thus, future studies stratifying patients by their molecular subtypes may give much more power to classic case control studies, and genes of no or borderline significance may appear to be high-penetrant for certain subtypes and, therefore, be identifiable.