Alterations in Retinal Microvascular Geometry in Young Type 1 Diabetes

OBJECTIVE - To describe retinal microvascular geometric parameters in young patients with type 1 diabetes. RESEARCH DESIGN AND METHODS - Patients with type 1 diabetes (aged 12-20 years) had clinical assessments and retinal photography following standardized protocol at a tertiary-care hospital in Sydney. Retinal microvascular geometry, including arteriolar and venular tortuosity, branching angles, optimality deviation, and length-to-diameter ratio (LDR), were measured from digitized photographs. Associations of these geometric characteristics with diabetes duration, A1C level, systolic blood pressure (SBP), and other risk factors were assessed. RESULTS - Of 1,159 patients enrolled, 944 (81.4%) had gradable photographs and 170 (14.7%) had retinopathy. Older age was associated with decreased arteriolar (P = 0.024) and venular (P = 0.002) tortuosity, and female subjects had larger arteriolar branching angle than male subjects (P = 0.03). After adjusting for age and sex, longer diabetes duration was associated with larger arteriolar branching angle (P ≤ 0.001) and increased arteriolar optimality deviation (P = 0.018), higher A1C was associated with increased arteriolar tortuosity (>8.5 vs. ≤8.5%, P = 0.008), higher SBP was associated with decreased arteriolar LDR (P = 0.002), and higher total cholesterol levels were associated with increased arteriolar LDR (P = 0.044) and decreased venular optimality deviation (P = 0.044). These associations remained after controlling for A1C, retinal vessel caliber, and retinopathy status and were seen in subjects without retinopathy. CONCLUSIONS - Key diabetes-related factors affect retinal microvascular geometry in young type 1 diabetes, even in those without evidence of retinopathy. These early retinal alterations may be markers of diabetes microvascular complications. © 2010 by the American Diabetes Association.link_to_OA_fulltex

Whole genome analysis of clouded leopard species reveals an ancient divergence and distinct demographic histories

Similar to other apex predator species, populations of mainland (Neofelis nebulosa) and Sunda (Neofelis diardi) clouded leopards are declining. Understanding their patterns of genetic variation can provide critical insights on past genetic erosion and a baseline for understanding their long-term conservation needs. As a step toward this goal, we present draft genome assemblies for the two clouded leopard species to quantify their phylogenetic divergence, genome-wide diversity, and historical population trends. We estimate that the two species diverged 5.1 Mya, much earlier than previous estimates of 1.41 Mya and 2.86 Mya, suggesting they separated when Sundaland was becoming increasingly isolated from mainland Southeast Asia. The Sunda clouded leopard displays a distinct and reduced effective population size trajectory, consistent with a lower genome-wide heterozygosity and SNP density, relative to the mainland clouded leopard. Our results provide new insights into the evolutionary history and genetic health of this unique lineage of felids

Riboflavin alleviates cardiac failure in Type I diabetic cardiomyopathy

Heart failure (HF) is a common and serious comorbidity of diabetes. Oxidative stress has been associated with the pathogenesis of chronic diabetic complications including cardiomyopathy. The ability of antioxidants to inhibit injury has raised the possibility of new therapeutic treatment for diabetic heart diseases. Riboflavin constitutes an essential nutrient for humans and animals and it is an important food additive. Riboflavin, a precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), enhances the oxidative folding and subsequent secretion of proteins. The objective of this study was to investigate the cardioprotective effect of riboflavin in diabetic rats. Diabetes was induced in 30 rats by a single injection of streptozotocin (STZ) (70 mg /kg). Riboflavin (20 mg/kg) was orally administered to animals immediately after induction of diabetes and was continued for eight weeks. Rats were examined for diabetic cardiomyopathy by left ventricular (LV) remadynamic function. Myocardial oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD), the level of malondialdehyde (MDA) as well as heme oxygenase-1 (HO-1) protein level. Myocardial connective tissue growth factor (CTGF) level was measured by Western blot in all rats at the end of the study. In the untreated diabetic rats, left ventricular systolic pressure (LVSP) rate of pressure rose (+dp/dt), and rate of pressure decay (−dp/dt) were depressed while left ventricular end-diastolic pressure (LVEDP) was increased, which indicated the reduced left ventricular contractility and slowing of left ventricular relaxation. The level of SOD decreased, CTGF and HO-1 protein expression and MDA content rose. Riboflavin treatment significantly improved left ventricular systolic and diastolic function in diabetic rats, there were persistent increases in significant activation of SOD and the level of HO-1 protein, and a decrease in the level of CTGF. These results suggest that riboflavin treatment ameliorates myocardial function and improves heart oxidant status, whereas raising myocardial HO-1 and decreasing myocardial CTGF levels have beneficial effects on diabetic cardiomyopathy

The effect of Puerariae radix on lipoprotein metabolism in liver and intestinal cells

BACKGROUND: Animal studies investigating the beneficial effects of Puerariae radix on cardiovascular disease have suggested this plant possesses anti-diabetic and lipid lowering properties. However, the exact mechanism by which Puerariae radix affects lipid metabolism is currently unknown. The aim of this study was to investigate the effect of the water extract of Puerariae radix on the secretion of VLDL and chylomicrons from HepG2 liver cells and CaCo2 cells, respectively, in humans. METHODS: The amount of apoB(100 )(a protein marker for VLDL) and apoB(48 )(a protein marker for chylomicrons) in cells and media were quantified by Western Blotting and enhanced chemiluminescence (ECL). Total, free and esterified cholesterol concentrations were measured by gas liquid chromatography. RESULTS: Treatment of cells with water extract of Puerariae radix significantly decreased apoB(100 )production and secretion from HepG2 cells up to 66% in a dose dependent manner. The intracellular total cholesterol and free cholesterol concentration in HepG2 cells also decreased with increasing concentration of the Puerariae radix. In contrast, water extract of Puerariae radix attenuated apoB(48 )concentrations in cells, but not apoB(48 )secretion from CaCo2 enterocytes. CONCLUSIONS: Collectively, our findings suggest that the water extract of Puerariae radix attenuates the hepatic lipoprotein production and secretion. Our present cell culture findings may explain why circulating VLDL and LDL levels were attenuated in animals supplemented with Puerariae radix. Since decreasing the production and secretion of atherogenic lipoproteins decreases the risk of development of cardiovascular disease, diets supplemented with radix may provide a safe and effective beneficial cardioprotective effects in humans

Evaluation of host-derived volatiles for trapping Culicoides biting midges (Diptera: Ceratopogonidae)

Culicoides biting midges (Diptera: Ceratopognidae) cause pain and distress through blood feeding, and transmit viruses that threaten both animal and human health worldwide. There are few effective tools for monitoring and control of biting midges, with semiochemical-based strategies offering the advantage of targeting host-seeking populations. In previous studies, we identified the host preference of multiple Culicoides species, including Culicoides impunctatus, as well as cattle-derived compounds that modulate the behavioral responses of C. nubeculosus under laboratory conditions. Here, we test the efficacy of these compounds, when released at different rates, in attracting C. impunctatus under field conditions in Southern Sweden. Traps releasing 1-octen-3-ol, decanal, phenol, 4-methylphenol or 3-propylphenol, when combined with carbon dioxide (CO2), captured significantly higher numbers of C. impunctatus compared to control traps baited with CO2 alone, with low release rates (0.1 mg h−1, 1 mg h−1) being generally more attractive. In contrast, traps releasing octanal or (E)-2-nonenal at 1 mg h−1 and 10 mg h−1 collected significantly lower numbers of C. impunctatus than control traps baited with CO2 only. Nonanal and 2-ethylhexanol did not affect the attraction of C. impunctatus when compared to CO2 alone at any of the release rates tested. The potential use of these semiochemicals as attractants and repellents for biting midge control is discussed

Aquaglyceroporin-null trypanosomes display glycerol transport defects and respiratory-inhibitor sensitivity

Aquaglyceroporins (AQPs) transport water and glycerol and play important roles in drug-uptake in pathogenic trypanosomatids. For example, AQP2 in the human-infectious African trypanosome, Trypanosoma brucei gambiense, is responsible for melarsoprol and pentamidine-uptake, and melarsoprol treatment-failure has been found to be due to AQP2-defects in these parasites. To further probe the roles of these transporters, we assembled a T. b. brucei strain lacking all three AQP-genes. Triple-null aqp1-2-3 T. b. brucei displayed only a very moderate growth defect in vitro, established infections in mice and recovered effectively from hypotonic-shock. The aqp1-2-3 trypanosomes did, however, display glycerol uptake and efflux defects. They failed to accumulate glycerol or to utilise glycerol as a carbon-source and displayed increased sensitivity to salicylhydroxamic acid (SHAM), octyl gallate or propyl gallate; these inhibitors of trypanosome alternative oxidase (TAO) can increase intracellular glycerol to toxic levels. Notably, disruption of AQP2 alone generated cells with glycerol transport defects. Consistent with these findings, AQP2-defective, melarsoprol-resistant clinical isolates were sensitive to the TAO inhibitors, SHAM, propyl gallate and ascofuranone, relative to melarsoprol-sensitive reference strains. We conclude that African trypanosome AQPs are dispensable for viability and osmoregulation but they make important contributions to drug-uptake, glycerol-transport and respiratory-inhibitor sensitivity. We also discuss how the AQP-dependent inverse sensitivity to melarsoprol and respiratory inhibitors described here might be exploited

Cryptic Speciation in Brazilian Epiperipatus (Onychophora: Peripatidae) Reveals an Underestimated Diversity among the Peripatid Velvet Worms

Taxonomical studies of the neotropical Peripatidae (Onychophora, velvet worms) have proven difficult, due to intraspecific variation and uniformity of morphological characters across this onychophoran subgroup. We therefore used molecular approaches, in addition to morphological methods, to explore the diversity of Epiperipatus from the Minas Gerais State of Brazil.Our analyses revealed three new species. While Epiperipatus diadenoproctussp. nov. can be distinguished from E. adenocryptussp. nov. and E. paurognostussp. nov. based on morphology and specific nucleotide positions in the mitochondrial cytochrome c oxidase subunit I (COI) and small ribosomal subunit RNA gene sequences (12S rRNA), anatomical differences between the two latter species are not evident. However, our phylogenetic analyses of molecular data suggest that they are cryptic species, with high Bayesian posterior probabilities and bootstrap and Bremer support values for each species clade. The sister group relationship of E. adenocryptussp. nov. and E. paurognostussp. nov. in our analyses correlates with the remarkable morphological similarity of these two species. To assess the species status of the new species, we performed a statistical parsimony network analysis based on 582 base pairs of the COI gene in our specimens, with the connection probability set to 95%. Our findings revealed no connections between groups of haplotypes, which have been recognized as allopatric lineages in our phylogenetic analyses, thus supporting our suggestion that they are separate species.Our findings suggest high cryptic species diversity and endemism among the neotropical Peripatidae and demonstrate that the combination of morphological and molecular approaches is helpful for clarifying the taxonomy and species diversity of this apparently large and diverse onychophoran group

Intraocular pressure and aqueous humor flow during a euglycemic-hyperinsulinemic clamp in patients with type 1 diabetes and microvascular complications

<p>Abstract</p> <p>Background</p> <p>Microvascular complications, including retinopathy and nephropathy are seen with type 1 diabetes. It is unknown whether functional changes in aqueous humor flow or intraocular pressure (IOP) develop in parallel with these complications. This study was designed to test the hypothesis that clinical markers of microvascular complications coexist with the alteration in aqueous humor flow and IOP.</p> <p>Methods</p> <p>Ten patients with type 1 diabetes and ten healthy age- and weight-matched controls were studied. Aqueous flow was measured by fluorophotometry during a hyperinsulinemic-euglycemic clamp (insulin 2 mU/kg/min). Intraocular pressure was measured by tonometry at -10, 90 and 240 minutes from the start of the clamp, and outflow facility was measured by tonography at 240 minutes.</p> <p>Results</p> <p>During conditions of identical glucose and insulin concentrations, mean aqueous flow was lower by 0.58 μl/min in the diabetes group compared to controls (2.58 ± 0.65 versus 3.16 ± 0.66 μl/min, respectively, mean ± SD, p = 0.07) but statistical significance was not reached. Before the clamp, IOP was higher in the diabetes group (22.6 ± 3.0 mm Hg) than in the control group (19.3 ± 1.8 mm Hg, p = 0.01) but at 90 minutes into the clamp, and for the remainder of the study, IOP was reduced in the diabetes group to the level of the control group. Ocular pulse amplitude and outflow facility were not different between groups. Systolic blood pressure was significantly higher in the diabetes group, but diastolic and mean arterial pressures were not different.</p> <p>Conclusions</p> <p>We conclude that compared to healthy participants, patients with type 1 diabetes having microalbuminuria and retinopathy have higher IOPs that are normalized by hyperinsulinemia. During the clamp, a reduction in aqueous flow was not statistically significant.</p

A Multi-Host Agent-Based Model for a Zoonotic, Vector-Borne Disease. A Case Study on Trypanosomiasis in Eastern Province, Zambia

Background: This paper presents a new agent-based model (ABM) for investigating T. b. rhodesiense human African trypanosomiasis (rHAT) disease dynamics, produced to aid a greater understanding of disease transmission, and essential for development of appropriate mitigation strategies. Methods: The ABM was developed to model rHAT incidence at a fine spatial scale along a 75 km transect in the Luangwa Valley, Zambia. The method offers a complementary approach to traditional compartmentalised modelling techniques, permitting incorporation of fine scale demographic data such as ethnicity, age and gender into the simulation. Results: Through identification of possible spatial, demographic and behavioural characteristics which may have differing implications for rHAT risk in the region, the ABM produced output that could not be readily generated by other techniques. On average there were 1.99 (S.E. 0.245) human infections and 1.83 (S.E. 0.183) cattle infections per 6 month period. The model output identified that the approximate incidence rate (per 1000 person-years) was lower amongst cattle owning households (0.079, S.E. 0.017), than those without cattle (0.134, S.E. 0.017). Immigrant tribes (e.g. Bemba I.R. = 0.353, S.E.0.155) and school-age children (e.g. 5–10 year old I.R. = 0.239, S.E. 0.041) were the most at-risk for acquiring infection. These findings have the potential to aid the targeting of future mitigation strategies. Conclusion: ABMs provide an alternative way of thinking about HAT and NTDs more generally, offering a solution to the investigation of local-scale questions, and which generate results that can be easily disseminated to those affected. The ABM can be used as a tool for scenario testing at an appropriate spatial scale to allow the design of logistically feasible mitigation strategies suggested by model output. This is of particular importance where resources are limited and management strategies are often pushed to the local scale. © 2016 Alderton et al