Cellular targets of anti-alpha-enolase autoantibodies of patients with autoimmune retinopathy

Autoantibodies against alpha-enolase are often associated with visual loss in patients with autoimmune retinopathy. Anti-recoverin autoantibodies have been the most extensively studied for their pathologic association with cancer-associated retinopathy (CAR). It has been shown that anti-recoverin antibodies penetrate retinal layers corresponding to the cellular location of recoverin and cause the death of photoreceptors and bipolar cells. However, the pathogenic effects of anti-alpha-enolase antibodies have not been studied. In this study, we tested the labeling and apoptotic effects of such autoantibodies on retinal cells. Serum antibodies against alpha-enolase from patients with autoimmune retinopathy were tested ex vivo and in vivo in Sprague-Dawley rats. Autoantibodies to alpha-enolase specifically labeled the retinal ganglion cells and inner nuclear layer cells. Using ex vivo experiments and intravitreal injections, we observed that antibodies were capable of penetrating retinal tissue to target ganglion cell and inner nuclear layers and, consequently, were able to induce cell death through an apoptotic process. The apoptotic nuclei detected by a DNA fragmentation assay and caspase 3-positive cells were co-localized in the ganglion cell layer and inner nuclear layer. The results showed that antibodies against alpha-enolase target antigens in these layers and induce the apoptotic death of sensitive cells. Rat retinal explants and the intravitreal injection of antibodies provide us with a good model to identify antibody pathogenic targets in the retina. Such identification may help explain the complex of clinical symptoms for autoimmune retinopathy mediated by autoantibody and may help guide treatment strategies.     

Lateral branchial cyst--case report

A case report of big lateral branchial cyst growing for 25 years is described. The diagnosis was based on ultrasonography with aspiration biopsy, computed tomography and histopathological findings. Successful surgical treatment was performed. Rarity of big size and long duration of the disease is emphasized.     

Sonographic assessment of the liver in children with psoriasis

PURPOSE: The aim of this study was to compare the size and echotexture of the liver in psoriatic and healthy children. METHODS: In 70 psoriatic and 43 healthy children, longitudinal sonograms of the liver were obtained along standardized section planes defined by the anterior axillary line, medioclavicular line, and midline. The livers' size and echotexture were examined and compared between the study groups. RESULTS: The measurements of the liver along the 3 section planes were not significantly different between psoriatic and healthy children. Parenchymal liver echogenicity in psoriatic children was neither decreased nor increased. CONCLUSIONS: No abnormality in size or echotexture of the liver was found in the psoriatic children.     

Effect of 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors (statins) on tissue paraoxonase 1 and plasma platelet activating factor acetylhydrolase activities

The authors investigated the effect of pravastatin and fluvastatin on paraoxonase 1 (PON1) activity in plasma, liver, heart, and kidney, as well as on plasma platelet activating factor acetylhydrolase (PAF-AH) in the rat. The animals received pravastatin at doses of 4 and 40 mg/kg/d or fluvastatin at doses of 2 or 20 mg/kg/d for 3 weeks. Fluvastatin (20 mg/kg/d) reduced plasma PON1 activity toward paraoxon and phenyl acetate by 23.6% and 17.4%, respectively. The lower dose of this drug as well as both doses of pravastatin had no effect on plasma PON1. PON1 activity toward paraoxon in the liver of rats treated with 20 mg/kg/d fluvastatin was 27.5% lower than in the control group, and the activity toward phenyl acetate was reduced by 25.4% and 35.9% in rats receiving 2 and 20 mg/kg/d of this drug, respectively. Fluvastatin at 2 and 20 mg/kg/d also decreased cardiac PON1 by 31.3% and 27.3%, respectively. Both statins reduced PON1 activity in the renal cortex and medulla. Statins had no effect on plasma PAF-AH. It is concluded that fluvastatin reduces PON1 activity more efficiently than does pravastatin. Reducing effect on PON1 may negatively modulate atheroprotective potential of statins and may contribute to differences in antiatherosclerotic properties of different drugs in this group.     

Synthesis and cardiovascular activity of new 8-alkylamino-1,3-dimethyl-7-(2-hydroxy-3- piperazinopropyl)-3,7-dihydro-1H-purine-2,6-diones

7-{2-Hydroxy-3-[4-(2-phenoxyethyl)-piperazinyl-1-yl]-propyl}-1,3-di-methyl-3,7-dihydro-1H-purine-2,6-dione dihydrochloride (2), and several of its 8-alkylamino substituted derivatives (11-17) were synthesized and tested for electrocardiographic, antiarrhythmic and hypotensive activity. Also their alpha(1)- and alpha(2)-adrenoreceptor affinities were determined. It was found that compound 2, and its analogue 15 with 8-(2-morpholin-4-yl-ethylamino) substituent displayed a strong prophylactic antiarrhythmic activity in experimentally induced arrhythmia (LD50/ED50 = 54.9 and 55.0, respectively). The hypotensive activity was observed for 8-benzylamino (11) or 8-(pyridin-2-yl-methylamino) (12) analogues. All the new derivatives (11-17) and 2 showed a weak affinity for alpha1-(Ki = 0.225-1.400 microM) and alpha2-(Ki = 0.152-4.299 microM) receptors.     

Calcium channel antagonists attenuate cross-sensitization to the locomotor effects of nicotine and ethanol in mice

The present study was focused on evaluation of locomotor cross-sensitization between nicotine and ethanol in mice. First, we demonstrated that, after 5 daily injections, nicotine (0.5 mg/kg, ip) produced sensitization to its own locomotor stimulant effect. Moreover, nicotine-experienced mice manifested an enhanced response to ethanol challenge (2 g/kg, ip) indicating the development of cross-sensitization between nicotine and ethanol in mice. Additionally, the L-type voltage-dependent calcium channel antagonists: verapamil and diltiazem, but not nimodipine, at the dose of 20 mg/kg, injected before the ethanol challenge, blocked the expression of this cross-sensitization. These findings support the hypothesis that similar neural calcium-dependent mechanisms are involved in the sensitization to locomotor stimulant effects of nicotine and ethanol and point to certain differences in acute behavioral effects of various classes of calcium channel inhibitors.     

Evidence for progression in frontal cortical pathology in late-stage Huntington's disease

Atrophy of the cerebral cortex in Huntington's disease is regionally heterogeneous and progressive, involving the entire cerebral mantle in terminal stages. Here, two areas (9 and 46) of the dorsolateral prefrontal cortex were analyzed in 11 late-stage (grades 3 or 4) Huntington's diseased patients and 8 normal control subjects. We used a 3-dimensional cell counting method to assess laminar cell density, number, and width. Reductions in overall cortical thickness in areas 9 (26%) and 46 (23%) were comparable. Area 9 exhibited loss of projection neurons in layers III (16%), V (31%), and VI (37%); these same layers were also reduced in width (25%, 34%, and 46%, respectively). In area 46, reductions in cortical width in layers II (18%) and VI (35%) were not accompanied by neuronal loss. Glial density was increased in deeper layers, reaching significance in layer VI (68%) of area 9 and in layer V (75%) of area 46; glial number was not altered. Thus, area 46 exhibited marked cortical thinning without apparent neuronal degeneration, whereas in area 9 neuronal loss was pronounced, consistent with an advanced phase of cortical pathology. Prominent involvement of corticothalamic neurons is discussed in the context of striatal loop circuitry and a possible pathologic cascade of cortical degeneration.     

An attempt to use Gore-Tex surgical membrane in lumbar disc surgery

BACKGROUND: Peridural fibrosis developing after lumbar discectomy may be responsible for as much as 20% of all Failed Back Surgery Syndrome. A variety of biological and non-biological materials have been used as a barrier to invasion of fibrous tissue into the vertebral canal. AIM: The purpose of this study was to evaluate the use of expanded polytetrafluoroethylene (ePTFE) surgical membrane (Gore-Tex membrane) to inhibit peridural fibrosis and reduce FBSS symptoms after lumbar discectomy. MATERIAL AND METHODS: In a prospective study we compared postoperative results in 20 patients who had an ePTFE membrane implanted during lumbar discectomy with the results in 20 patients in whom no material was implanted. The outcomes were evaluated using a questionnaire on activities of daily living according to the Low Back Outcome Score, pain grading scale -- Visual Analog Scale, assessment of Lasegue sign and MRI 18-24 months after the operation for all patients. RESULTS: The authors found no evident positive clinical and radiological effects of using ePTFE surgical membrane during lumbar discectomy. CONCLUSIONS: 1. It is impossible to prove that ePTFE membrane used during lumbar discectomy essentially prevents postoperative peridural scar formation. 2. The use of ePTFE membrane does not improve the outcome of the surgical treatment of lumbar disc herniation.     

Analysis of phacoemulsification complications during mastering of the method

PURPOSE: Intra-operative and postoperative complications of the first 50 phacoemulsifications were evaluated. The procedures were performed by one, skilled at ECCE surgeon. The phaco-chop technique was carried out in all cases with use of anterior chamber maintainer (ACM). MATERIAL AND METHODS: Eyes for surgery met the requirements: normal comea, presence of red reflex from the fundus and correct lens position. The patients were divided into 2 groups: I group--25 eyes had first surgery, II group--25 eyes had second surgery. On the first day after surgery complications and uncorrected acuity were evaluated. RESULTS: 50 eyes of 48 patients underwent operation. The mean age was 69.4 years 5% eyes had previous surgical record: 4--underwent trabeculectomy, 1--pars plana vitrectomy. The 12 intra-operative complications appeared in 10 eyes (20%): posterior capsule rupture without vitreous loss in 4% and 10% with vitreous loss, Descemet membrane detachment in 4%, iris dialysis in 2%, and persistent iris damage without sphincter disruption in 4%. The 16 postoperative complications concerned 10 eyes (20%): corneal oedema in 20%, transient intra-ocular pressure raise in 8%, hyphaema in 2%, and fibrin exudation in 2%. The majority of complications concerned the I group of eyes. The uncorrected visual acuity was 0.5 or better in 80% of eyes, on the first day after the operation. CONCLUSIONS: The use of ACM made the first steps in phacoemulsification rate during the learning course.