Reversal of pentylenetetrazol-induced potentiation phenomenon by theta pulse stimulation in the CA1 region of rat hippocampal slices

The effect of theta pulse stimulation (TPS) on pentylenetetrazol (PTZ)-induced long-term potentiation of population spikes was studied in the CA1 region of rat hippocampal slices. The field excitatory postsynaptic potential (fEPSP) and population spikes (PS) were recorded from strata radiatum and pyramidale, respectively, following stimulation of Schaffer collaterals. A transient PTZ application produced a long-lasting enhancement of PS amplitude. A 3-min episode of TPS delivered at test-pulse intensity failed to reverse the PTZ potentiation. However, the same stimulation at a higher intensity produced complete reversal of the PTZ potentiation when delivered during the last minutes of PTZ application. Prior application of high-intensity TPS also decreased the amount of PTZ potentiation, whereas it had no long-lasting effect on baseline synaptic responses. High-intensity TPS induced reversal was blocked by adenosine A1 receptor antagonist and, furthermore, was reduced by protein phosphatase 1 inhibitor. The results suggest that mechanism of PTZ-induced LTP reversal involves activation of adenosine receptors and protein phosphatases.     

Mitomycin C reduces corneal light scattering after excimer keratectomy

PURPOSE: To evaluate the effect of intraoperative mitomycin C (MMC) on corneal light scattering after excimer laser keratectomy. METHODS: Phototherapeutic keratectomy (PTK) was performed in 24 rabbit eyes. After 40-microm epithelial ablation, animals were divided into three groups. In group 1, filter paper discs soaked with MMC (group 1A, 0.5 mg/mL; group 1B, 0.25 mg/ml) were applied for 1 minute. In group 2, annular filter papers soaked with MMC (group 2A, 0.5 mg/mL; group 2B, 0.25 mg/mL) were applied for 1 minute. Controls received vehicle only (group 3). Six-millimeter diameter 100-microm deep PTK was performed. Corneal light scattering was measured weekly from 1 to 6 weeks, at 10 weeks, and at 8 and 13 months using a scatterometer. A corneal light scattering index (SI) ranging from 0 to 10 was calculated; SI of 1 represents normal scattering. RESULTS: A statistically significant decrease in mean SI was noted in group 2A (annular MMC 0.5 mg/mL; p<0.05) as compared with the control group at 2 weeks. At 10 weeks, SI approached baseline levels in group 2 and the control group but showed significant increase in group 1 (MMC disc; p < 0.05). At 8 and 13 months, SI showed no statistical differences between groups. CONCLUSIONS: Controlled application of 0.5 mg/mL MMC in the corneal midperiphery transiently reduces corneal light scattering after excimer keratectomy in this rabbit model.     

Corneal neovascularization

Corneal neovascularization (NV) is a sight-threatening condition usually associated with inflammatory or infectious disorders of the ocular surface. It has been shown in the field of cancer angiogenesis research that a balance exists between angiogenic factors (such as fibroblast growth factor and vascular endothelial growth factor) and anti-angiogenic molecules (such as angiostatin, endostatin, or pigment epithelium derived factor) in the cornea. Several inflammatory, infectious, degenerative, and traumatic disorders are associated with corneal NV, in which the balance is tilted towards angiogenesis. The pathogenesis of corneal NV may be influenced by matrix metalloproteinases and other proteolytic enzymes. New medical and surgical treatments, including angiostatic steroids, nonsteroidal inflammatory agents, argon laser photocoagulation, and photodynamic therapy have been effective in animal models to inhibit corneal NV and transiently restore corneal "angiogenic privilege."     

Further refinement of Pendred syndrome locus by homozygosity analysis to a 0.8 cM interval flanked by D7S496 and D7S2425.

Pendred syndrome is an autosomal recessive disease characterised by congenital sensorineural deafness and goitre. The gene responsible for Pendred syndrome has been mapped to chromosome 7q31 in a 5.5 centimorgan (cM) interval flanked by D7S501 and D7S523. This interval was recently refined a to 1.7 cM interval located between D7S501 and D7S692. In the present study, we report linkage analysis data on a large consanguineous family genotyped with eight microsatellite markers located between D7S501 and D7S523. Complete cosegregation with the disease locus was observed with the loci analysed, which further supports locus homogeneity for Pendred syndrome and close linkage to this region. Haplotype analysis placed the Pendred syndrome gene between D7S496 and D7S2425 in a 0.8 cM interval. This additional refinement of the Pendred syndrome region will facilitate the construction of a physical map of the region and will help the identification of candidate genes.     

IL-6 Levels,Nutritional Status,and Mortality in Prevalent Hemodialysis Patients

Summary

Background and objectives

The influence of serum IL-6 levels on nutritional status in chronic hemodialysis (HD) patients remains to be elucidated. The present report describes a prospective longitudinal study of IL-6 levels and nutritional parameters to determine whether high IL-6 levels are independently associated with nutritional status over time in a cohort of prevalent hemodialysis patients.

Design, setting, participants, & measurements

85 clinically stable hemodialysis patients (37.6% women), with a mean age of 66.5 ± 10.6 years, were studied after exclusion of patients with BMI < 20 kg/m² and/or serum albumin <35 g/L. IL-6, dietary energy and protein intake, and biochemical markers of nutrition and body composition (anthropometry and bioimpedance analysis) were measured at baseline and at 6, 12, 18, and 24 months following enrollment. Observation of this cohort was continued over 2 additional years.

Results

IL-6 levels increased with time in both unadjusted (linear estimate: 2.57 ± 0.44 pg/ml per 2 yrs; P = 0.001) and adjusted models (linear estimate: 2.35 ± 0.57 pg/ml per 2 yrs; P = 0.049). Significant reductions of daily energy intake, laboratory markers (albumin, transferrin, cholesterol, creatinine), and body composition (fat mass) with higher IL-6 levels were observed over the duration of the longitudinal observation period. However, none of the studied parameters were associated with changes in IL-6 levels over time (IL-6-by-time interactions were NS). Furthermore, cumulative incidences of survival were correlated with the baseline serum IL-6 levels (P = 0.004 by log-rank test). Finally, for each pg/ml increase in IL-6 level, the hazard ratio for death from all causes was 1.06 (95% CI 1.01 to 1.10) after adjustment for demographic and clinical parameters.

Conclusions

Our results suggest that higher serum IL-6 levels are associated with all-cause mortality without additional changes in clinical and laboratory markers of nutritional status in clinically stable HD patients.     

Double-knot transscleral suture fixation technique for displaced intraocular lenses

PURPOSE: To describe a simplified new technique for repositioning and attaching a suture to the haptic of a displaced posterior chamber intraocular lens (IOL). METHODS: We describe a double-knot technique for repositioning and transscleral suture fixation of a subluxed posterior chamber IOL after penetrating keratoplasty. Two 10-0 Prolene transscleral sutures on straight needles are passed around the IOL haptic, tied extraocularly, and used to secure the repositioned haptic of the IOL. A second knot ties the transscleral suture in the scleral bed, stabilizing the haptic in the ciliary sulcus. RESULTS: In the case described, the IOL was stable and well positioned 2 months after surgery. CONCLUSION: The double-knot technique for intraocular repositioning and transscleral suture fixation of displaced posterior chamber IOLs reduces the extensive intraocular manipulation and scleral incisions required for IOL exchange and may reduce chronic irritation associated with iris fixation.