Integrated carbon, sulfur, and nitrogen isotope chemostratigraphy of the Ediacaran Lantian Formation in South China: Spatial gradient, ocean redox oscillation, and fossil distribution.

The Ediacaran Doushantuo Formation in South China is a prime target for geobiological investigation because it offers opportunities to integrate chemostratigraphic and paleobiological data. Previous studies were mostly focused on successions in shallow-water shelf facies, but data from deep-water successions are needed to fully understand basinal redox structures. Here, we report δ13 Ccarb , δ13 Corg , δ34 Spyr , δ34 SCAS , and δ15 Nsed data from a drill core of the fossiliferous Lantian Formation, which is a deep-water equivalent of the Doushantuo Formation. Our data confirm a large (>10‰) spatial gradient in δ13 Ccarb in the lower Doushantuo/Lantian formations, but this gradient is probably due to the greater sensitivity of carbonate-poor deep-water sediments to isotopic mixing with 13 C-depleted carbonate cements. A pronounced negative δ13 Ccarb excursion (EN3) in the upper Doushantuo/Lantian formations, however, is spatially consistent and may be an equivalent of the Shuram excursion. δ34 Spyr is more negative in deeper-water facies than in shallow-water facies, particularly in the lower Doushantuo/Lantian formations, and this spatial pattern is interpreted as evidence for ocean redox stratification: Pyrite precipitated in euxinic deep waters has lower δ34 Spyr than that formed within shallow-water sediments. The Lantian Formation was probably deposited in oscillating oxic and euxinic conditions. Euxinic black shales have higher TOC and TN contents, but lower δ34 Spyr and δ15 Nsed values. In euxinic environments, pyrite was predominantly formed in the water column and organic nitrogen was predominantly derived from nitrogen fixation or NH4+ assimilation because of quantitative denitrification, resulting in lower δ34 Spyr and δ15 Nsed values. Benthic macroalgae and putative animals occur exclusively in euxinic black shales. If preserved in situ, these organisms must have lived in brief oxic episodes punctuating largely euxinic intervals, only to be decimated and preserved when the local environment switched back to euxinia again. Thus, taphonomy and ecology were the primary factors controlling the stratigraphic distribution of macrofossils in the Lantian Formation.

Hydrogen Isotopic Composition of Arctic and Atmospheric CH4 Determined by a Portable Near-Infrared Cavity Ring-Down Spectrometer with a Cryogenic Pre-Concentrator.

In this study, near-infrared continuous wave cavity ring-down spectroscopy was applied to the measurement of the δ2H of methane (CH4). The cavity ring-down spectrometer (CRDS) system consisted of multiple DFB laser diodes to optimize selection of spectral line pairs. By rapidly switching measurements between spectral line peaks and the baseline regions, the long-term instrumental drift was minimized, substantially increasing measurement precision. The CRDS system coupled with a cryogenic pre-concentrator measured the δ2H of terrestrial atmospheric CH4 from 3 standard liters of air with a precision of ±1.7‰. The rapidity with which both C and H isotopic measurements of CH4 can be made with the CRDS will enable hourly monitoring of diurnal variations in terrestrial atmospheric CH4 signatures that can be used to increase the resolution of global climate models for the CH4 cycle. Although the current instrument is not capable of measuring the δ2H of 10 ppbv of martian CH4, current technology does exist that could make this feasible for future spaceflight missions. As biological and abiotic CH4 sources have overlapping carbon isotope signatures, dual-element (C and H) analysis is key to reliable differentiation of these sources. Such an instrument package would therefore offer improved ability to determine whether or not the CH4 recently detected in the martian atmosphere is biogenic in origin. Key Words: Arctic-Hydrogen isotopes-Atmospheric CH4-CRDS-Laser. Astrobiology 16, 787-797.

IL15 levels on day 7 after hematopoietic cell transplantation predict chronic GVHD.

Chronic GVHD (cGVHD) is an important complication of allogeneic hematopoietic cell transplantation (HCT). As preemptive therapy might be efficacious if administered early post transplant, we set out to determine whether cGVHD can be predicted from the serum level of a biomarker on day 7 or 28. In a discovery cohort of 153 HCT recipients conditioned with BU, fludarabine and rabbit antithymocyte globulin (ATG), we determined serum levels of B-cell-activating factor, vascular endothelial growth factor, soluble TNF-α receptor 1, soluble IL2 receptor α, IL5, IL6, IL7, IL15, γ-glutamyl transpeptidase, cholinesterase, total protein, urea and ATG. Patients with low levels of IL15 (<30.6 ng/L) on day 7 had 2.7-fold higher likelihood of developing significant cGVHD (needing systemic immunosuppressive therapy) than patients with higher IL15 levels (P<0.001). This was validated in a validation cohort of 105 similarly-treated patients; those with low IL15 levels had 3.7-fold higher likelihood of developing significant cGVHD (P=0.001). Low IL15 was not associated with relapse; it trended to be associated with acute GVHD and was associated with low infection rates. In conclusion, low IL15 levels on day 7 are predictive of cGVHD, and thus could be useful in guiding preemptive therapy.

Challenges for coring deep permafrost on Earth and Mars.

A scientific drilling expedition to the High Lake region of Nunavut, Canada, was recently completed with the goals of collecting samples and delineating gradients in salinity, gas composition, pH, pe, and microbial abundance in a 400 m thick permafrost zone and accessing the underlying pristine subpermafrost brine. With a triple-barrel wireline tool and the use of stringent quality assurance and quality control (QA/QC) protocols, 200 m of frozen, Archean, mafic volcanic rock was collected from the lower boundary that separates the permafrost layer and subpermafrost saline water. Hot water was used to remove cuttings and prevent the drill rods from freezing in place. No cryopegs were detected during penetration through the permafrost. Coring stopped at the 535 m depth, and the drill water was bailed from the hole while saline water replaced it. Within 24 hours, the borehole iced closed at 125 m depth due to vapor condensation from atmospheric moisture and, initially, warm water leaking through the casing, which blocked further access. Preliminary data suggest that the recovered cores contain viable anaerobic microorganisms that are not contaminants even though isotopic analyses of the saline borehole water suggests that it is a residue of the drilling brine used to remove the ice from the upper, older portion of the borehole. Any proposed coring mission to Mars that seeks to access subpermafrost brine will not only require borehole stability but also a means by which to generate substantial heating along the borehole string to prevent closure of the borehole from condensation of water vapor generated by drilling.

Hydrogeologic controls on episodic H2 release from precambrian fractured rocks--energy for deep subsurface life on earth and mars.

Dissolved H(2) concentrations up to the mM range and H(2) levels up to 9-58% by volume in the free gas phase are reported for groundwaters at sites in the Precambrian shields of Canada and Finland. Along with previously reported dissolved H(2) concentrations up to 7.4 mM for groundwaters from the Witwatersrand Basin, South Africa, these findings indicate that deep Precambrian Shield fracture waters contain some of the highest levels of dissolved H(2) ever reported and represent a potentially important energy-rich environment for subsurface microbial life. The delta (2)H isotope signatures of H(2) gas from Canada, Finland, and South Africa are consistent with a range of H(2)-producing water-rock reactions, depending on the geologic setting, which include both serpentinization and radiolysis. In Canada and Finland, several of the sites are in Archean greenstone belts characterized by ultramafic rocks that have under-gone serpentinization and may be ancient analogues for serpentinite-hosted gases recently reported at the Lost City Hydrothermal Field and other hydrothermal seafloor deposits. The hydrogeologically isolated nature of these fracture-controlled groundwater systems provides a mechanism whereby the products of water-rock interaction accumulate over geologic timescales, which produces correlations between high H(2) levels, abiogenic hydrocarbon signatures, and the high salinities and highly altered delta (18)O and delta (2)H values of these groundwaters. A conceptual model is presented that demonstrates how periodic opening of fractures and resultant mixing control the distribution and supply of H(2) and support a microbial community of H(2)-utilizing sulfate reducers and methanogens.

Oxidation of the Ediacaran ocean.

Oxygenation of the Earth's surface is increasingly thought to have occurred in two steps. The first step, which occurred approximately 2,300 million years (Myr) ago, involved a significant increase in atmospheric oxygen concentrations and oxygenation of the surface ocean. A further increase in atmospheric oxygen appears to have taken place during the late Neoproterozoic period ( approximately 800-542 Myr ago). This increase may have stimulated the evolution of macroscopic multicellular animals and the subsequent radiation of calcified invertebrates, and may have led to oxygenation of the deep ocean. However, the nature and timing of Neoproterozoic oxidation remain uncertain. Here we present high-resolution carbon isotope and sulphur isotope records from the Huqf Supergroup, Sultanate of Oman, that cover most of the Ediacaran period (approximately 635 to approximately 548 Myr ago). These records indicate that the ocean became increasingly oxygenated after the end of the Marinoan glaciation, and they allow us to identify three distinct stages of oxidation. When considered in the context of other records from this period, our data indicate that certain groups of eukaryotic organisms appeared and diversified during the second and third stages of oxygenation. The second stage corresponds with the Shuram excursion in the carbon isotope record and seems to have involved the oxidation of a large reservoir of organic carbon suspended in the deep ocean, indicating that this event may have had a key role in the evolution of eukaryotic organisms. Our data thus provide new insights into the oxygenation of the Ediacaran ocean and the stepwise restructuring of the carbon and sulphur cycles that occurred during this significant period of Earth's history.

Intravitreal triamcinolone with photodynamic therapy for subfoveal choroidal neovascularisation in age related macular degeneration.

AIMS: To report the effects of intravitreal triamcinolone acetonide (iTAAC) injections as an adjunctive treatment to photodynamic therapy (PDT) with verteporfin for new subfoveal choroidal neovascularisation (CNV) in age related macular degeneration (AMD). METHODS: We retrospectively reviewed the records of all AMD patients who had iTAAC within 6 weeks of their first PDT and had a follow up of one year or longer. The proportion of eyes after one year follow up that lost or gained >or=15 and >or=30 ETDRS letters, baseline and one year lesion greatest linear dimension (GLD), number of PDTs, and side effects were assessed. RESULTS: Fourteen patients were evaluated. Eleven received one initial combined treatment and three received an additional combined treatment after 6 months. Median follow up was 18 months (range 12 to 25 months). Overall, 7% gained >or=30 letters, 50% maintained stable vision, 14% lost 15-29 letters, and 29% lost >or=30 letters. Overall, mean GLD increased from 2580 (SD 1088) microm to 3946 (SD 1503) micro m (p = 0.01). The mean number of PDTs during the first year was 2.57. Side effects were mild intraocular pressure elevation in 28.5% and cataract progression in 50% of phakic eyes. CONCLUSIONS: iTAAC with PDT in AMD was found to be relatively safe and had reasonable results for lesions with some classic component.

The effects of dorzolamide on choroidal and retinal perfusion in non-exudative age related macular degeneration.

AIM: To comprehensively evaluate the effects of dorzolamide on the choroidal and retinal circulation in patients with age related macular degeneration (AMD). METHODS: In this randomised, double masked, parallel study, 36 non-exudative AMD patients were randomised in a 2 to 1 fashion to placebo versus topical dorzolamide and underwent assessment of their choroidal and retinal circulation. Scanning laser ophthalmoscope indocyanine green angiograms (ICGA) were analysed by a new area dilution analysis technique. Four areas in the perifoveal region and two areas in the temporal peripapillary region were evaluated by plotting intensity of fluorescence of each area over time. The means of the choroidal filling times and the heterogeneity of the filling times were assessed. Scanning laser ophthalmoscope fluorescein angiography (FA) was evaluated for retinal arteriovenous passage (AVP) times by plotting intensity of fluorescence of retinal vessels over time. Assessment was performed at baseline and at 4 months. RESULTS: Compared to placebo, AMD patients treated with dorzolamide showed a significantly increased rapidity of choroidal filling in the superior and inferior peripapillary regions (p=0.007, p=0.02, respectively). No significant difference in choroidal filling times was found in any of the perifoveal areas (p=0.9). Also, on FA assessment, treatment with dorzolamide showed no statistical differences in AVP times (p=0.19). CONCLUSIONS: Dorzolamide may increase peripapillary choroidal perfusion in non-exudative AMD patients. Further studies are merited.

Transpupillary thermotherapy for subfoveal occult choroidal neovascularization: effect on ocular perfusion.

PURPOSE: To perform a descriptive analysis of the effects on ocular blood flow of transpupillary thermotherapy (TTT) for occult subfoveal choroidal neovascular membranes (CNVMs) in age-related macular degeneration (AMD). METHODS: Eleven subjects with occult subfoveal CNVM due to AMD were assessed in a masked fashion by color Doppler imaging (CDI) within 24 hours before, 24 hours after, and 1 month after undergoing TTT. RESULTS: In the posterior ciliary arteries (PCAs), there were no statistically significant changes observed in the peak systolic velocity (PSV), end diastolic velocity (EDV), or resistive index (RI) at 24 hours. At 1 month, the mean EDV decreased 36% (P = 0.0105) and the mean RI increased 3.8% (P = 0.0305) in the nasal PCA. Although there was a similar trend in the temporal PCA, the differences did not reach statistical significance. In the central retinal artery (CRA), the mean PSV decreased 16% (P = 0.0137), and the mean EDV decreased 21% (P = 0.0222) at 24 hours after treatment. There were no statistically significant differences in the CRA blood flow indices at 1 month after treatment. In the ophthalmic artery, there were no statistically significant differences observed in the mean PSV, EDV, or RI at 24 hours or 1 month after treatment. CONCLUSIONS: TTT is associated with transiently decreased volumetric blood flow in the retinal circulation 24 hours after treatment. In the posterior ciliary arteries that supply the choroid, there were no changes observed at 24 hours, but at 1 month, there was a decrease in the mean EDV and an increase in the RI in the nasal and temporal PCAs, reaching statistical significance in the nasal PCA only. This study suggests that TTT could lead to alterations in choroidal blood flow, as assessed by CDI. Further study is warranted.

Relation between dietary intake, serum concentrations, and retinal concentrations of lutein and zeaxanthin in adults in a Midwest population.

BACKGROUND: Information on concentrations of retinal carotenoids (macular pigment, or MP) is of particular interest because MP protects against age-related macular degeneration, the leading cause of irreversible blindness in the United States. OBJECTIVE: This study was designed to evaluate the relation between dietary intake, blood concentrations, and retinal concentrations of carotenoids in a large group of volunteers. DESIGN: Two hundred eighty volunteers in the Indianapolis area completed health and diet questionnaires, donated a blood sample, and participated in MP density assessment to determine retinal carotenoid status. Dietary intake was assessed by food-frequency questionnaire. Serum concentrations of lutein, zeaxanthin, and beta-carotene were measured by HPLC. MP optical density (MPOD) was determined psychophysically with a 460-nm, 1 degrees test stimulus. RESULTS: Average MPOD was 0.21 +/- 0.13. Average intakes of lutein + zeaxanthin and beta-carotene were 1101 +/- 838 and 2935 +/- 2698 microg/d, respectively. Although several key dietary intake variables (eg, lutein + zeaxanthin and beta-carotene) differed by sex, no significant sex differences were found in either serum concentrations of lutein and zeaxanthin or MPOD. Serum beta-carotene concentrations were significantly higher in women than in men. Serum lutein + zeaxanthin and dietary intake of lutein + zeaxanthin were significantly correlated and significantly related to variations in MPOD (r = 0.21, P < 0.001, and r = 0.25, P < 0.001, respectively). CONCLUSIONS: Retinal carotenoids can be measured in epidemiologic studies. In this study, MPOD was associated with lutein + zeaxanthin in the diet and the serum. Retinal concentrations, however, were influenced by other factors as well. To understand the effect of dietary lutein + zeaxanthin intake on the retina and risk of age-related eye disease, future studies should include measures of macular concentrations of these pigments.

Asymmetric synthesis of BB-3497--a potent peptide deformylase inhibitor.

By screening a library of metalloenzyme inhibitors, the N-formyl-hydroxylamine derivative BB-3497 was identified as a potent inhibitor of Escherichia coli peptide deformylase with antibacterial activity both in vitro and in vivo. The homochiral synthesis of BB-3497, involving a novel asymmetric Michael addition reaction is described.

Glomerular permselectivity factors are not responsible for the increase in fractional clearance of albumin in rat glomerulonephritis.

The increased fractional clearance of albumin in nephrotic states has long been attributed to glomerular permselectivity dysfunction. Using radiolabeled rat serum albumin, transferrin, IgG, and polydisperse Ficoll, this study investigated the changes in their in vivo fractional clearance in puromycin aminonucleoside nephrosis and anti-glomerular basement membrane glomerulonephritis. In control rats the lack of charge selectivity was confirmed by the demonstration that carboxymethyl Ficoll (valence approximately -39) had the same fractional clearance as uncharged Ficoll. Both diseases exhibited similar effects on fractional clearance measurements suggesting an underlying common mechanism. In disease, there was good agreement between the fractional clearance of proteins determined by radioactivity as compared to those determined by radioimmunoassay. A small increase in the fractional clearance for IgG was evident in disease as compared to controls, which mirrored the change in the equivalent size Ficoll, suggesting that the increase is because of the development of a small proportion of large pores in the glomerular capillary wall. There was no increase, however, in the fractional clearance of Ficoll of equivalent size to albumin in either disease, yet the fractional clearance of the albumin increased by 12 to 14 times as determined by radioactivity and 4500 to 6600 times as determined by radioimmunoassay. This study demonstrates that glomerulonephritis is not a disease associated with changes in glomerular permeability to albumin but is because of alterations in albumin processing by cells distal to the glomerular basement membrane. It is also apparent that approaches to glomerular pathology and proteinuria as risk factors in renal disease must be reassessed.

The return of glomerular filtered albumin to the rat renal vein--the albumin retrieval pathway.

BACKGROUND: Recent studies have demonstrated that the normal glomerular capillary wall (GCW) is not charge selective to albumin. This means that albumin flux across the GCW is high. This has been confirmed in studies where albumin uptake by the tubules has been inhibited. Therefore, there must be a high capacity postglomerular retrieval pathway in normal kidneys that returns filtered albumin back to the blood supply. METHODS: This study identifies the presence of glomerular filtered albumin in the renal vein from the analysis of the decrease of radioactivity in the venous effluent after the injection of a pulse of tritium labeled albumin into the renal artery in vivo and in the isolated perfused kidney (IPK). RESULTS: The glomerular filtered albumin is returned to the blood supply by a high capacity pathway that transports this albumin at a rate of 1830+/-292 microg/min rat kidney (n= 14) (mean+/-SEM). This pathway has been identified under physiological conditions in vivo and in the IPK. The pathway is specific for albumin as it does not occur for horseradish peroxidase (HRP). The pathway is inhibited in a non-filtering kidney. The pathway is also inhibited by NH4Cl, an inhibitor of protein uptake. CONCLUSIONS: The high capacity retrieval pathway for albumin is most likely associated with transtubular cell transport. It is also apparent that most albuminuric states could be accounted for by the malfunctioning of this pathway without resorting to any change in glomerular permselectivity.

Macular pigment optical density before and after cataract extraction.

PURPOSE: Psychophysical methods of measuring macular pigment (MP) use comparisons of short- and midwave light in the fovea and parafovea to derive optical density estimates. This light must pass through the crystalline lens before absorption by the MPs can occur. The effect of lens absorption on these measures has not been adequately determined. The present study assesses the influence of lens absorption on MP measurements by comparing MP optical density (MPOD) measured before and after cataract extraction. METHODS: MPOD was measured using flicker photometry in free view at 458 nm with a 1 degrees stimulus. Twenty-nine eyes from 24 patients with cataracts sufficiently severe to require cataract extraction were evaluated. RESULTS: In the entire group of 24 patients, the mean (+/-SD) age measured 68.7 +/- 9.5 years, and the mean MPOD measured 0.19 +/- 0.11. For all 29 eyes measured, MPOD averaged 0.206 +/- 0.13 before and 0.18 +/- 0.12 after cataract extraction. MPOD measurements at the two time points (mean 8.1 +/- 4.7 weeks after surgery) were highly correlated (r = +0.58), suggesting that a cataractous lens does not influence the MP measurement technique. CONCLUSIONS: Psychophysical techniques can be used to obtain reliable measurements of MP in elderly subjects, even in those with cataracts. Moreover, differences in retinal illuminance due to varying opaqueness of the crystalline lens do not seem to have a measurable influence on MPOD.

Ab initio analysis of lithium dimethylaminoborohydride.

Ab initio calculations were used to determine the equilibrium geometries and energies of lithium dimethylaminoborohydride. Relative energies of the monomeric and dimeric species were calculated in the gas phase and for the dimethyl ether microsolvated molecules. The most stable structure was a dimer in which the lithium and boron atoms were bridged by two hydrogen atoms, similar to the three-center two-electron bonds in diborane. This hydrogen bridging was maintained in the lithium dimethylaminoborohydride bis(dimethyl ether) microsolvate.

Macular pigment optical density in a midwestern sample.

OBJECTIVE: To assess the distribution of the macular pigments (MPs) lutein (L) and zeaxanthin (Z) in a healthy sample more representative of the general population than past studies and to determine which dietary factors and personal characteristics might explain the large interindividual differences in the density of these MPs. DESIGN: Prevalence study in a self-selected population. PARTICIPANTS: Two hundred eighty healthy adult volunteers, consisting of 138 men and 142 women, between the ages of 18 and 50 years, recruited from the general population. METHODS: MP optical density was measured psychophysically at 460 nm by use of a 1 degrees test field. Serum was analyzed for carotenoid and vitamin E content with reversed-phase high-performance liquid chromatography. Usual intakes of nutrients over the past year were determined by means of a food frequency questionnaire. MAIN OUTCOME MEASURES: MP optical density. RESULTS: Mean MP optical density measured 0.211 +/- 0.13, which is approximately 40% lower than the average reported in smaller, less representative studies. MP density was 44% lower in the bottom versus the top quintile of serum L and Z concentrations. Similarly, MP density was 33% lower in the bottom compared with the top quintile of L and Z intake. MP density was 19% lower in blue-grey-eyed subjects than in subjects with brown-black irises. When all variables were considered together in a general linear model of determinants of MP, statistically significant (P < 0.05) relationships were found between MP density and serum L and Z, dietary L and Z intake, fiber intake, and iris color. CONCLUSIONS: These data suggest that MP values in this healthy adult population are lower than in smaller select samples. Moreover, these data indicate that MP is related to serum L and Z, dietary L and Z intake, fiber intake, and iris color.

Ramipril and aminoguanidine restore renal lysosomal processing in streptozotocin diabetic rats.

AIMS/HYPOTHESIS: We aimed to examine the time course for the diabetes-related changes in renal lysosomal processing and to determine whether these changes can be prevented by aminoguanidine or ramipril treatment. METHODS: The percentage desulphation of intravenously injected tritium labelled dextran sulphate ([3H]DSO4) in the urine, as determined by ion-exchange chromatography, was used as a marker of lysosomal sulphatase activity. Sulphatase activity was determined 1, 2, 3 and 4 weeks after the onset of diabetes in rats as well as in rats treated with either aminoguanidine or ramipril for twelve weeks. RESULTS: The amount of totally desulphated [3H]DSO4 in urine collected from control rats was 65.6 +/- 0.8%. This was significantly reduced in diabetic rats two (57.4 +/- 1.4% desulphated), three (56.8 +/- 1.3 % desulphated) and four (52.9 +/- 2.2% desulphated) weeks after the onset of diabetes. The significant decrease in the amount of totally desulphated [3H]DSO4 in the urine also found at 12 weeks after the onset of diabetes was not affected by drug treatment. There was no significant difference in the amount of partially desulphated [3H]DSO4 in the urine between all the study groups. However, the increase in totally sulphated [3H]DSO4 in the urine collected from diabetic rats (8.7 +/- 1.7 % sulphated) compared with that of control rats (2.2 +/- 0.5% sulphated) was normalised by treatment with both aminoguanidine (4.8 +/- 1.6% sulphated) or ramipril (4.5 +/- 0.8% sulphated). CONCLUSIONS/INTERPRETATION: These results raise the possibility that the diabetes-induced changes in renal lysosomal processing may be one of the initial events in the development of diabetic nephropathy. Aminoguanidine and ramipril, known for their different mechanism of action, seem to prevent diabetes-induced changes in lysosomal processing either through their effects on enzyme activity within the lysosome or through their effects on the trafficking of molecules to and from the lysosome.

Intravitreal triamcinolone acetonide in exudative age-related macular degeneration.

PURPOSE: To examine the effects of intravitreal injection of 4.0 mg triamcinolone acetonide on the visual and clinical course of exudative age-related macular degeneration. METHODS: A randomized clinical trial of a single injection of triamcinolone acetonide into the vitreous cavity of experimental eyes at baseline versus observation of untreated subjects was performed in 27 patients followed up for 6 months. Inclusion criteria included exudative age-related macular degeneration with subfoveal or occult choroidal neovascularization, and visual acuity between 20/40 and 20/400. Examination, acuity assessment, fundus photography, and fluorescein angiography were performed at baseline and at 3 and 6 months after enrollment. LogMAR visual acuity was compared between groups by a repeated measures analysis of variance model. Masked assessment of photographic studies was performed and groups were compared with Fisher's exact test. RESULTS: Visual acuity was significantly better in the treated group compared with control subjects at 3 and 6 months (P < 0.005). Fundus photography and angiography were more likely to show stability or improvement at 3 and 6 months in the treated group (P = 0.05). Intraocular pressure elevation was seen in 25% of treated patients, but was controlled with topical medications. Progression of cataract was more frequently seen in the treated group. CONCLUSIONS: Intravitreal triamcinolone acetonide may provide short-term improvement in visual acuity and fundus findings in exudative macular degeneration. These findings must be considered preliminary and should be followed by multicenter, masked, placebo-controlled trials with long-term follow-up.

Olestra consumption is not associated with macular pigment optical density in a cross-sectional volunteer sample in Indianapolis.

The associations between the intake of the fat-substitute olestra and the concentrations of macular carotenoid pigments and serum lutein and zeaxanthin were investigated in a volunteer cross-sectional sample in Indianapolis. The study was conducted in January through March, 1998 after olestra-containing savory snacks had been sold in central Indiana for a year. Volunteers (n = 280) aged 18-50 y were recruited to make a single clinic visit during which macular pigment optical density (MPOD) was determined by psychophysical flicker photometry, serum was obtained for determination of lutein and zeaxanthin concentration, usual intake of olestra, carotenoids and nutrients were assessed by 1-y food frequency questionnaire, and health habits including smoking, physical characteristics such as eye color, demographics and medical history were determined by questionnaire. Intake of olestra at least one time per month for the past year was reported by 81:280 subjects and their mean, median and 90(th) percentile intakes were 1.09, 0.34 and 2.43 g olestra/d, respectively. Mean macular pigment optical density was not significantly different between olestra consumers and nonconsumers (0.213 +/- 0.014 vs. 0.211 +/- 0.010) nor was serum lutein and zeaxanthin concentration (0.361 +/- 0.017 vs. 0.375 +/- 0. 013 micromol/L) or intake (1242 +/- 103 mg/d vs. 1042 +/- 58 mg/d) in one-way or two-way ANOVA. Olestra intake was not associated with MPOD or serum lutein and zeaxanthin before or after correction for significant covariates of MPOD. Thus, olestra intake over the past year in a cross-sectional volunteer sample in Indianapolis was not associated with MPOD.

Prevention of albuminuria by aminoguanidine or ramipril in streptozotocin-induced diabetic rats is associated with the normalization of glomerular protein kinase C.

This study examined whether the prevention of diabetes-related albuminuria by aminoguanidine (AG) or ramipril (RAM) may be mediated by a common post-glomerular basement membrane renal intracellular mechanism involving protein kinase C (PKC). The renal handling of albumin was examined over 24 weeks in control and streptozotocin (STZ)-induced diabetic rats. A radioimmunoassay (RIA) that measures intact albumin, and intravenously injected tritium-labeled rat serum albumin, was used to assess the proportion of intact albumin and albumin fragments in urine. Diabetes was induced in male Sprague-Dawley rats by the intravenous administration of STZ at a dose of 50 mg/kg. Age-matched control rats received buffer alone. Diabetes was characterized by an increase in blood glucose (>15 mmol/l), an increase in GHb (means at 24 weeks 29.3+/-1.1%; control 6.1+/-0.1%, P<0.005), an increase in glomerular filtration rate (GFR) (4.13+/-0.15 ml/min; control 3.54+/-0.19 ml/min, P<0.005), an increase in intact albumin excretion rate (expressed as geometric mean 11.64 times/divided by 2.11 mg/24 h; control 0.74 times/divided by 1.57 mg/24 h, P<0.005) as measured by RIA, and an increase in glomerular PKC activity (26.83+/-2.38 pmol x mg(-1) x min(-1); control 14.6+/-2.99 pmol x mg(-1) x min(-1), P<0.005). Treatment of diabetic rats with either AG or RAM prevented the rise in intact albuminuria and glomerular PKC activity. Renal lysosomal cathepsin activity decreased in diabetic rats and this was not prevented by AG or RAM. Neither drug affected glycemic control or GFR, but RAM reduced systolic blood pressure (BP), whereas AG did not. These data indicate that urinary excretion of intact albumin and albumin-derived fragments in diabetes may be modulated independently of glycemic control (AG and RAM) and systolic BP (RAM). While both drugs are known for their different mechanisms of action, the fact that both prevent diabetes-related increases in glomerular PKC activity and albuminuria supports the hypothesis that PKC plays a central role in the development of diabetic nephropathy.