Hepatocyte destruction with enhanced collagen synthesis: characteristic feature of chronic hepatitis C patients on haemodialysis.

Hepatitis C virus (HCV) infection is frequent among patients with end-stage renal disease on haemodialysis and is considered to be an independent risk factor for mortality in this setting. However, only a few of these patients are treated with anti-hepatitis virus treatment before the development of end-stage renal disease. Recent guidelines recommend identification of patients with good prognoses who are in need of interferon treatment, but we know little of patients who must be treated urgently. Ninety-eight patients on haemodialysis (48 anti-HCV-positive and 50 anti-HCV-negative patients) were enrolled in this study; HCV RNA was detected in 43 anti-HCV-positive patients. Univariate analysis and multivariate regression analysis were applied to identify variables independently associated with persistent HCV infection. Seven variables were proven to be associated with persistent HCV infection. Among them, type IV collagen 7S and N-terminal propeptide of type III procollagen (P-III-P) were defined as independent variables useful in distinguishing HCV RNA-positive patients from HCV RNA-negative patients with 0.91 sensitivity, 0.91 specificity, 0.89 positive predictive value and 0.93 negative predictive value. Our observations suggest that hepatocyte destruction with enhanced liver fibrosis is a characteristic clinical feature of persistent HCV infection. Type IV collagen 7S of ≥ 5 ng/mL and/or P-III-P of ≥ 5 U/mL would be useful markers to identify patients in need of interferon treatment, which supports the idea of the Kidney Disease: Improving Global Outcomes guidelines that a good prognosis in patients with HCV infection on haemodialysis should prompt consideration for IFN treatment when applicable.

Theoretical studies to understand surface chemistry on carbon anodes for lithium-ion batteries: reduction mechanisms of ethylene carbonate.

Reductive decomposition mechanisms for ethylene carbonate (EC) molecule in electrolyte solutions for lithium-ion batteries are comprehensively investigated using density functional theory. In gas phase the reduction of EC is thermodynamically forbidden, whereas in bulk solvent it is likely to undergo one- as well as two-electron reduction processes. The presence of Li cation considerably stabilizes the EC reduction intermediates. The adiabatic electron affinities of the supermolecule Li(+)(EC)n (n = 1-4) successively decrease with the number of EC molecules, independently of EC or Li(+) being reduced. Regarding the reductive decomposition mechanism, Li(+)(EC)n is initially reduced to an ion-pair intermediate that will undergo homolytic C-O bond cleavage via an approximately 11.0 kcal/mol barrier, bringing up a radical anion coordinated with Li(+). Among the possible termination pathways of the radical anion, thermodynamically the most favorable is the formation of lithium butylene dicarbonate, (CH2CH2OCO2Li)2, followed by the formation of one O-Li bond compound containing an ester group, LiO(CH2)2CO2(CH2)2OCO2Li, then two very competitive reactions of the further reduction of the radical anion and the formation of lithium ethylene dicarbonate, (CH2OCO2Li)2, and the least favorable is the formation of a C-Li bond compound (Li carbides), Li(CH2)2OCO2Li. The products show a weak EC concentration dependence as has also been revealed for the reactions of LiCO3(-) with Li(+)(EC)n; that is, the formation of Li2CO3 is slightly more favorable at low EC concentrations, whereas (CH2OCO2Li)2 is favored at high EC concentrations. On the basis of the results presented here, in line with some experimental findings, we find that a two-electron reduction process indeed takes place by a stepwise path. Regarding the composition of the surface films resulting from solvent reduction, for which experiments usually indicate that (CH2OCO2Li)2 is a dominant component, we conclude that they comprise two leading lithium alkyl bicarbonates, (CH2CH2OCO2Li)2 and (CH2OCO2Li)2, together with LiO(CH2)2CO2(CH2)2OCO2Li, Li(CH2)2OCO2Li and Li2CO3.

Polyol metabolism of retrograde axonal transport in diabetic rat large optic nerve fiber.

PURPOSE: The role of the polyol pathway metabolism in progressive impairment of retrograde axonal transport was evaluated in the optic nerve of rats with streptozotocin-induced diabetes. METHODS: Rats with streptozotocin-induced diabetes received a low (3 mg/kg body weight) or high dose (10 mg/kg body weight) of oral aldose reductase inhibitor (ARI). At 1 and 3 months after induction of diabetes, Fluoro-Gold (FG, Chemicon, Temecula, CA) was injected into the dorsal lateral geniculate nucleus. Percentages of FG-labeled large, medium, and small retinal ganglion cells (RGCs) per total population were calculated in the retinas of ARI-treated diabetic, untreated diabetic, and normal control rats. RESULTS: Mean percentages of FG-labeled large RGCs per total population were significantly decreased in nontreated diabetic rats compared with control animals at 1 month of induced diabetes. This decrease in FG labeling was not observed in both the low- and high-dose ARI-treated diabetic rats. At 3 months of induced diabetes, FG labeling of both large and medium RGCs was significantly decreased. This decrease was completely ameliorated by high-dose ARI treatment. CONCLUSIONS: These results indicate that diabetes affects retrograde axonal transport progressively through selective impairment of RGCs and that the polyol pathway metabolism is involved in such impairment.

Ophthalmic artery blood flow velocity changes in diabetic patients as a manifestation of macroangiopathy.

PURPOSE: The hemodynamic characteristics of ophthalmic artery (OA) blood flow velocity in diabetic patients with ocular involvement were evaluated. METHODS: Changes in OA blood flow of eyes with background diabetic retinopathy (BDR), proliferative retinopathy (PDR) and ocular ischemic syndrome (OIS) were analyzed by Color Doppler imaging. RESULTS: Patients with BDR and PDR had significantly lower diastolic and mean blood flow velocities and higher pulsatility indices compared to controls. Diabetic patients with OIS had significantly lower systolic, diastolic and mean anterograde OA blood flow velocities than the controls. Pulsatility indices were higher in anterograde OA blood flow measurements compared to controls. Systolic blood flow velocities in rubeotic eyes with OIS were significantly lower than in rubeotic eyes with PDR. CONCLUSION: OA blood flow measurements by color doppler imaging may detect macroangiopathies in diabetic patients as manifested by carotid atheromas and arterio- and atherosclerosis of the OA and its branches.

Isolation and characterization of a new denitrifying spirillum capable of anaerobic degradation of phenol.

Two kinds of phenol-degrading denitrifying bacteria, Azoarcus sp. strain CC-11 and spiral bacterial strain CC-26, were isolated from the same enrichment culture after 1 and 3 years of incubation, respectively. Both strains required ferrous ions for growth, but strain CC-26 grew better than strain CC-11 grew under iron-limited conditions, which may have resulted in the observed change in the phenol-degrading bacteria during the enrichment process. Strain CC-26 grew on phenol, benzoate, and other aromatic compounds under denitrifying conditions. Phylogenetic analysis of 16S ribosomal DNA sequences revealed that this strain is most closely related to a Magnetospirillum sp., a member of the alpha subclass of the class Proteobacteria, and is the first strain of a denitrifying aromatic compound-degrading bacterium belonging to this group. Unlike previously described Magnetospirillum strains, however, this strain did not exhibit magnetotaxis. It grew on phenol only under denitrifying conditions. Other substrates, such as acetate, supported aerobic growth, and the strain exhibited microaerophilic features.

Retrograde axonal transport impairment of large- and medium-sized retinal ganglion cells in diabetic rat.

PURPOSE: Several abnormalities in visual pathway functions in diabetic humans and animals have been reported. We demonstrated retrograde axonal transport impairment in retinal ganglion cells of streptozotocin-diabetic rats. METHODS: Diabetes was induced in male Wistar albino rats by intraperitoneal injection of streptozotocin. Three months after the induction of diabetes, fluoro-gold was injected into the dorsal lateral geniculate nucleus. Percentages of fluoro-gold-labeled large-, medium- and small-sized retinal ganglion cells per total population were calculated in wholemount retinas of diabetic and control rats. The same sections were stained with cresyl violet and each retinal ganglion cell type evaluated by light microscopy. RESULTS: Although a quantitative decrease in the population of each retinal ganglion cell type was not observed, mean percentages of fluoro-gold-labeled large- and medium-sized retinal ganglion cells per total population were significantly decreased in diabetic rats compared with controls. CONCLUSIONS: Our results suggest that diabetes affects the retrograde axonal transport in large- and medium-sized retinal ganglion cells despite the absence of morphological changes in the perikaryon and decrease in total cell population. Diabetes-induced impairment of retrograde axonal transport in large- and medium-sized retinal ganglion cells precede optic nerve involvement. However, this may merely be a consequence of metabolic changes in diabetic states.

Blood-aqueous barrier disruption in experimental anterior segment ischemia in rabbit eyes.

The blood-aqueous barrier (BAB) in experimentally induced anterior segment ischemia (ASI) following strabismus or retinal detachment surgery in pigmented rabbits was evaluated by laser flare photometry. Four simultaneous rectus tenotomies produced a significantly higher flare value on the 1st postoperative day. Obstruction of one or two vortex veins produced significantly high flare values on the 1st and 3rd postoperative days. Scleral buckling with interference of one vortex vein produced a higher flare value than that with buckling alone. Interference of three vortex veins by diathermy and the encircling procedure produced serious ASI. Disruption of BAB in ASI can be detected quantitatively with laser flare photometry. Introduction of prostaglandin synthetase inhibitor resulted in a significant reduction of flare values following surgery. Prostaglandin synthetase inhibitor can partly ameliorate BAB disruption.

Ocular ischemic syndrome in diabetic patients.

PURPOSE: Diabetes mellitus aggravates carotid occlusive disease, that can manifest as ocular ischemic syndrome (OIS). Ocular manifestations and visual prognosis of OIS in diabetic patients were retrospectively analyzed. METHODS: Twenty-three consecutive diabetic patients with OIS were divided into two groups according to the presence of iris neovascularization, and the clinical features were reviewed. RESULTS: In the first group, 14 eyes of 12 diabetic patients (11 men and 1 woman) had no iris neovascularization. Two patients had bilateral OIS. The ages in this group ranged from 50-75 years. Four eyes with optic atrophy or ischemic optic neuropathy had severe visual loss. Six eyes with hypoperfusion retinopathy or retinal vein obstruction and 2 eyes with cataract had mild visual loss. Each eye with amaurosis fugax or retinal neovascularization had no visual deterioration. Asymmetrical retinopathy was observed in 2 patients. Carotid surgery stabilized and resolved amaurosis fugax and hypoperfusion retinopathy. In the second group, 11 eyes of 11 patients had iris neovascularization. The patients were all male and their ages ranged from 53-77 years. All eyes with iris neovascularization had severe visual deterioration. In 5 patients, asymmetrical ocular manifestation was observed. Carotid reconstruction surgery and ophthalmological treatment were not successful for recovering a satisfactory visual outcome in OIS. CONCLUSION: The features of OIS in diabetic patients mimic diabetic retinopathy and manifest with asymmetrical ocular findings. Iris neovascularization is an indicator of poor visual prognosis. It is essential to recognize the early stages of OIS associated with diabetes mellitus.

Effect of aminoguanidine on optic nerve involvement in experimental diabetic rats.

The effect of aminoguanidine (AG) on structural abnormalities in optic nerve fibers was evaluated in streptozotocin-induced diabetic rats. Morphometry of myelinated optic nerve fibers showed a partial amelioration on the reduction of the axon size but complete preservation of myelin size with low dose (25 mg kg-1 body weight) AG treatment. High dose (100 mg kg-1 body weight) AG completely prevented myelinated nerve fiber atrophy. These findings indicated that nonenzymatic glycation contributes to the development of optic nerve changes in diabetic rats.

Structural impairments in optic nerve of diabetic rats ameliorated with the aldose reductase inhibitor.

Structural impairments of optic nerve fibers in the streptozotocin-induced diabetic rat were investigated using morphometric analysis. The effect of aldose reductase inhibitor (ARI) on abnormalities in myelinated nerve fibers was also evaluated. Three months after the induction of diabetes, loss of body weight and significantly elevated levels of serum glucose were observed. Light microscopic examination revealed that the mean size of the optic nerve in the diabetic rat remained unchanged. Electron microscopic morphometry showed the significantly smaller cross-sectional size of axons and myelin but no change of myelinated fiber number. Reductions of myelinated fiber size was especially remarkable in the larger fibers. ARI treatment improved structural abnormalities without any changes in body weight and blood glucose level. Reduction of axon size and myelin/axon ratio was completely inhibited by ARI treatment. These findings suggest that structural impairment may contribute to the abnormalities of psychophysical and electrophysiological measurements detected in diabetes. Moreover, ARI treatment, which can improve the polyol metabolism, may have a beneficial effect on optic nerve impairment in diabetes.

Iridopathy in eyes with proliferative diabetic retinopathy: detection of early stage of rubeosis iridis.

Forty-two eyes of 31 proliferative diabetic retinopathy patients with laser flare intensity > or = 20 photon counts/ms underwent fluorescein iris angiography to evaluate any changes in the blood-iris barrier and iris biomicroscopy to detect rubeosis iridis. Fluorescein iris angiography revealed abnormal dye leakage in all eyes. Laser flare intensity significantly correlated with the degree of dye leakage. Eyes with dye leakage from only the pupillary border had no rubeosis. In 11 out of 18 (61%) eyes with moderate dye leakage, proliferative diabetic iridopathy with early rubeosis was present in 8 and advanced iridopathy in 3 eyes. In all eyes with excessive leakage, rubeosis iridis was detected under slitlamp examination. High laser flare intensity has a close relationship with advanced blood-ocular barrier disruption. High flare intensity may be a helpful indicator in detecting incipient rubeosis or advanced diabetic iridopathy.

Determination of trace amounts of albumin in human bronchoalveolar lavage fluids by fluorometry with chromazurol S.

Fluorometry using chromazurole S (CAS) was applied to determine trace amounts of albumin in human bronchoalveolar lavage fluids (BALF). The calibration curve was linear in the range of 5-60 micrograms/ml of albumin. The CAS method was proven to be much more selective for albumin than for IgG. Freezing of BALF samples did not affect albumin analysis by the CAS method after storage at -20 degrees C for 80 days. This finding suggests that albumin in the BALF samples is stable under these conditions. The correlation was highly linear (r = 0.966) between the albumin levels in concentrated BALF samples (n = 47) determined by the CAS method and by radial immunodiffusion. The CAS method is sensitive enough to determine albumin levels in unconcentrated BALF samples, whereas radial immunodiffusion often requires concentration. The former method is more suitable for measuring albumin in BALF samples than the latter, because concentration by ultrafiltration results in poor reproducibility. The concentration of albumin in BALF samples of healthy volunteers (n = 5) and patients with sarcoidosis (n = 32) was determined by the CAS method. There was a statistically significant difference (P < 0.01) in the albumin levels in BALF samples between healthy subjects and patients with sarcoidosis at a clinically active state (n = 15). This finding shows that the determination of albumin levels in BALF samples is useful for investigating lung diseases and that the CAS method is promising in the determination of trace albumin in BALF samples, because it is simple, sensitive and precise.

Laser flare intensity in diabetics: correlation with retinopathy and aqueous protein concentration.

The laser flare intensity in diabetics, measured with the scattering of a light beam, was evaluated and compared with actual aqueous protein concentration obtained during surgery. Measurement of the laser flare intensity in 120 diabetics and 108 normal subjects was performed with the laser flare cell meter (FC1000 Kowa, Tokyo). Aqueous protein concentration in 26 diabetics and six controls who underwent intraocular surgery was measured by the method of Bradford. No significant difference in the laser flare intensity was found between normal subjects and diabetics without retinopathy. A significant increase in the laser flare intensity was observed after six decades in diabetics with background retinopathy and all with proliferative retinopathy. The laser flare intensity correlated with the duration of diabetes mellitus. There was a significant linear relation between the laser flare intensity and actual aqueous protein concentration. The linear regression formula was X = Y1.39 x 1.02 (X = protein concentration, mg/dl; Y = flare intensity, photon counts/ms). The precise value of the laser flare intensity provides a new indicator to evaluate the diabetic change in the function of the ocular barrier.