Percentage Of Lesion Area Research Articles

Anti-ulcerogenic activity of the powder fraction of leaves of Aspillia africana against ethanol-induced gastric ulcer in rats: Possible role of mucus and antioxidant effect

Massive alcohol drinking can lead to gastric ulcer. In the present study we investigated the gastroprotective effect of powder fraction of the leaves of Apillia africana (AA) in ethanol (EtOH) induced oxidative stress and peptic ulcer in rats. The rats were divided into six treatment groups, which were the normal control group, negative control group (ethanol-induced) and tree treatment groups: AA at the doses of 100 mg/kg body weight (BW), 200 mg/kg BW and 400 mg/kg BW, and the positive control group treated with famotidin at the dose of 100 mg/kg BW. Gastroprotective effect was measured by the ulcerative lesion index, ulcer surface area, percentage of lesion area. Antioxidant and histopathological analyses were also conducted to gain additional data regarding the gastroprotective effect of AA in the rats’ stomachs. AA showed protected the gastric mucosa from ethanol ulceration, as revealed by the improved macroscopic and histological appearance. AA significantly increased the gastric homogenate content of GSH and inhibited the lipid peroxidation as revealed by the reduced gastric content of malondialdehyde (MDA). AA possesses gastro-protective activity, which could be attributed to a mucus production, antioxidant, and regeneration activities.

Gut microbiota may mediate the impact of chronic apical periodontitis on atherosclerosis in apolipoprotein E-deficient mice.

There are growing evidences linking chronic apical periodontitis (CAP) to atherosclerosis. Gut microbiota is found to be involved in the development of atherosclerosis. Recent studies have shown that CAP could change the diversity and composition of the gut microbiota. It was therefore, we hypothesized that gut microbiota and its metabolites could mediate the impact of CAP on atherosclerosis. Twenty-four 5-week-old lipoprotein E knockout (apoE-/- ) mice were randomly divided into four groups: the CAP group, Con group, Co-CAP (cohoused with CAP) and Co-Con (cohoused with Con) group. In the CAP group, sterile cotton wool containing P.gingivalis was placed into the exposed pulp chamber, followed by coronal resin-based composite restoration of the bilateral maxillary first and second molars. In the Con group, a sham operation was performed. Biweekly, mice in the CAP group were anaesthetised to check the sealing of coronal access. Meanwhile, the animals in the Con group were anaesthetised. The cohousing approach was used to introduce gut microbiota from the CAP and Con groups into the Co-CAP and Co-Con groups, respectively. Alterations in the abundance and diversity of the gut microbiota were detected using 16S rRNA sequencing, Oil-red O staining was used to demonstrate the extent of lesions, and serum levels of trimethylamine N-oxide (TMAO), and immunohistochemistry of flavin-containing monooxygenase 3 (FMO3) in liver were used to assess TMAO-related metabolic alterations. Alterations of alpha and beta diversity were shown both in the CAP and the Co-CAP groups. Moreover, the percentage of atherosclerotic lesion area increased in the CAP and Co-CAP groups (p < .05). Linear discriminant analysis effect size (LEfSe) at the family level found the increases of Lachnospiraceae and Ruminococcaceae (p < .05), which were positively correlated with serum TMAO levels (p < .05). In the redundancy analysis technique (RDA), serum levels of TMAO were positively associated with the atherosclerotic lesions. Co-occurrence analysis revealed that the relative abundances of Lachnospiraceae and Porphyromonadacae were positively correlated with both the percentage of lesion area and TMAO level (p < .05). Thus, within the limitations of this study, the data suggest that the gut microbiota can mediate the effects of CAP on atherosclerosis.

Efficacy and safety of HDL/apoA-1 mimetics on human and mice with atherosclerosis: a systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): the National Natural Science Foundation of China Background Low high-density lipoprotein cholesterol (HDL-C) level as a residual risk factor of cardiovascular disease (CVD) is still causing concern, although using chemical drugs for raising HDL-C level failed. The effect of high-density lipoprotein/ apolipiproteinA-1(HDL/apoA-1) mimetics on atherosclerosis is controversial. Aim In this meta-analysis we analyzed the effect of high-density lipoprotein/ apolipiproteinA-1(HDL/apoA-1) mimetics on atherosclerotic lesion both in human and mice. Methods We systematically searched PubMed, Cochrane, Web of Science and EMBASE databases up to June 6, 2020 for eligible studies using wide search terms and included all the publications meet the including criteria. The methodological quality of the human studies was assessed using Review Manager (RevMan) software (version 5.3.). The methodological quality of the mice studies was assessed by using stair list. WMD(SMD) with 95% CI was used as a measure of the association between HDL/apoA-1 mimetics and plaque regression in human (in mice), after pooling data across trials in a random effect model. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. STATA (version 14.0) was used to conduct all statistical analyses. Results We identified 15 randomized controlled trials in which 6 trails including 754 ACS (HDL/apoA-1 mimetics = 414, placebo = 340) patients used for efficacy analysis and all of 15 trails used for safety analysis and 17 controlled trials for animal study. The pooled results showed that the use of HDL/apoA-1 mimetics did not significant decreased the percent atheroma volume(p = 0.494) and total atheroma volume(p = 0.560) in patients with acute coronary syndrome (ACS). However, HDL/apoA-1 mimetics (or gene transfection) was significant associated with all of final percent lesion area, final lesion area and changes in lesion area (SMD, -1.75; 95% CI: -2.21∼-1.29, p = 0.000; SMD, -0.78; 95% CI: -1.18∼-0.38, p = 0.000; SMD: -2.06; 95% CI, -3.92∼-0.2, p = 0.03) in mice. Conclusions In human, HDL/apoA-1 mimetics cannot significantly improve atheroma volume in artery, although it is safe. However, in animal, the results suggest HDL/apoA-1 mimetics (or gene transfection) can decrease lesion area. So additional studies are needed to further investigate and explain the different efficacy of HDL/apoA-1 mimetic peptides between human and animal. Abstract Figure. Forest plots of human studies

Abstract P145: Renal Proximal Tubule-specific Renin Deficiency Has No Effect On Atherosclerosis In Hypercholesterolemic Mice

Objective: Renin cleaving angiotensinogen to release angiotensin I is the rate-limiting step to produce angiotensin II. Although juxtaglomerular cells are the predominant source of renin in circulation, renin protein is also present in proximal tubules. In this study, we investigated the effects of renin in proximal tubule cells (PTC) on development of atherosclerosis in hypercholesterolemic mice Approach and Result: Inducible PTC-specific renin deficient (PTC-renin -/-) mice were developed by breeding renin floxed mice with mice expressing Cre under the control of the N-myc downstream regulated gene 1 (Ndrg1-Cre ERT2). All study mice were in a low-density lipoprotein receptor (LDLR) deficient background, and both male and female littermates were studied. Littermates of renin floxed mice with or without Ndrg1-Cre ERT2 transgene were injected intraperitoneally with tamoxifen (150 mg/kg/day) for 5 consecutive days when they were 4-6 weeks old. Cre genotypes were determined after weaning (~ 3-4 weeks old) and deletion of renin gene in kidney was verified by PCR of DNA extracted from kidney after termination (~18-20 weeks old). Two weeks after the last injection of tamoxifen, mice were fed a Western diet for 12 weeks, which led to plasma total cholesterol concentrations above 1000 mg/dl (P = 0.893 in male and P = 0.192 in female between PTC-renin +/+ and -/- mice). PTC-specific renin deficiency did not affect blood pressure (PTC-renin+/+ vs -/-: 110 ± 1 mmHg vs 112 ± 1 mmHg in male, P = 0.452; and 105 ± 3mmHg vs 106 ± 2 mmHg in female, P = 0.875), as measured by a tail-cuff system. Atherosclerosis in the ascending and aortic arch regions was measured with an en face method. No differences on percent lesion area between the two genotypes in both male and female mice (PTC-renin+/+ vs -/-: 18.1 ± 1.4% vs 18.9 ± 1.5% in male, P = 0.315; and 16.2 ± 1.5% vs 16.2 ± 1.2% in female, P = 0.648). Conclusion: Renal proximal tubule-specific renin deficiency does not affect blood pressure and atherosclerosis in hypercholesterolemic mice.

Abstract P159: Induction Of Human Angiotensinogen In Hepatocytes And Human Renin In Renal Proximal Tubule Cells Does Not Accelerate Atherosclerosis In Mice

Objective: Hepatocyte-produced angiotensinogen (AGT) can be filtered by glomeruli and retained in renal proximal tubules. Renin protein has also been detected in proximal tubules (PTC) of kidney. However, it is unknown whether AGT and renin in proximal tubules contribute to atherosclerosis. This study aimed to determine whether hepatocyte-derived AGT interacts with renin in proximal tubules to promote atherosclerosis. Approach and Results: Transgenic mice expressing human renin driven by a kidney androgen-related protein promoter (KAP-hREN) in an LDLR -/- background were administered subcutaneously with testosterone (15 mg/mouse, constant release for 60 days) to activate the human renin transgene in PTCs. To induce synthesis of human AGT in hepatocytes, adeno-associated viral (AAV; 3 x 10 10 genomic copies/mouse) vector containing human AGT with a liver-specific promoter was injected intraperitoneally. Three groups of male littermates were administered testosterone: (1) wild type mice administered null AAV (n=11), (2) KAP-hREN transgenic mice administered null AAV (n=7), and (3) KAP-hREN transgenic mice (n=8) administered AAV containing human AGT. Two weeks after administration of testosterone and AAVs (either null or human AGT), all mice were fed a Western diet for 6 weeks. Induction of human renin was confirmed by mRNA abundance of human renin in kidney of KAP-hREN transgenic mice. In mice administered human AGT AAV, presence of human AGT was detected in plasma with a human AGT ELISA kit. Induction of both human AGT in liver and human renin in proximal tubules did not affect plasma cholesterol concentrations or systolic blood pressure. Atherosclerotic lesion sizes, as quantified by percent lesion area using an en face method, were not different among the 3 groups (Group 1 vs 2 vs 3: 3.7 ± 0.4% vs 3.3 ± 0.9% vs 2.3 ± 0.3%; P = 0.19). Conclusions: Induction of human AGT in hepatocytes and human renin in proximal tubules does not augment atherosclerosis in hypercholesterolemic mice.

&lt;p&gt;Gastroprotective Effect of DLBS2411 Bioactive Fraction from &lt;em&gt;Cinnamomum burmannii&lt;/em&gt; Against Ethanol-Induced Gastric Damage in Rats&lt;/p&gt;

BackgroundThe study was carried out to evaluate the anti-ulcerative and gastroprotective effect of DLBS2411, a bioactive fraction from Cinnamomum burmannii (Nees & T. Nees) Blume, in Wistar rats (Rattus norvegicus).MethodsThe rats were divided into five treatment groups, which were the Normal control group, Negative control group (ethanol-induced) and two treatment groups: DLBS2411 at the doses of 25 mg/kg body weight (BW) and 50 mg/kg BW, and the Positive control group treated with sucralfate at the dose of 100 mg/kg BW. Gastroprotective effect was measured by the ulcerative lesion index, ulcer surface area, percentage of lesion area, and cure ratio. Hematological and histopathological analyses were also conducted to gain additional data regarding the gastroprotective effect of DLBS2411 in the rats’ stomachs.ResultsDLBS2411 was found to contain not less than 15% of total phenolic compounds. Treatment with DLBS2411 at doses of 25 mg/kg BW and 50 mg/kg BW significantly reduced the percentage of ulcer area in rats. The percentage of ulcer area for the Negative control group and both doses in the DLBS2411 treatment group reached 22.64±6.82%, 6.75±4.41%, and 6.18±4.63%, respectively. Ulcer surface area in the treatment groups and Positive control group also decreased. Histopathological data showed that gastric epithelial cells in the Negative control group were more severely ulcerated than in the treatment group of DLBS2411 and the Positive control group.ConclusionThis study showed that DLBS2411 at the dose of 50 mg/kg BW was more effective in protecting the stomach lining than DLBS2411 at the dose of 25 mg/kg BW, as measured by percentage of ulceration inhibition and the ulcerative lesion index.

Evaluation of Detached Strawberry Leaves for Anthracnose Disease Severity Using Image Analysis and Visual Ratings

Inoculation of detached strawberry leaves with Colletotrichum species may provide an accurate, rapid, nondestructive method of identifying anthracnose-resistant germplasm. The purpose of this study was to statistically compare two methods (visual and image analysis) of evaluating disease severity of strawberry germplasm screened for anthracnose resistance. Detached leaves of 77 susceptible and resistant strawberry clones were inoculated with one Colletotrichum gloeosporioides (Penz.) Penz. &amp; Sacc. and two C. fragariae A. N. Brooks isolates. Anthracnose disease symptoms on each leaf were assessed quantitatively via computer-based image analysis to determine percentage lesion area and qualitatively by two independent raters using a visual disease severity rating scale (0 = no symptoms to 5 = entire leaf dead). The two visual raters’ average disease severity ratings (n = 3413) were in substantial agreement with a weighted Cohen’s kappa coefficient (k) of 0.80 [95% confidence interval (CI) 0.79–0.82]. There was a strong positive correlation between percent lesion area determined by image analysis and the visual disease scores of the two raters (rp = 0.79). Image analysis provided a precise measurement of percent lesion area of infected leaves while visual assessment provided more rapid results. Our results indicate that detached leaf inoculations can be used as a rapid preliminary screen to separate anthracnose-susceptible from -resistant germplasm in large populations within breeding programs. It also may be used for assessing the resistance/susceptibility of parental breeding lines to various Colletotrichum species and isolates, for mapping germplasm for resistance genes, and in pesticide development studies.

Applicability of Trichoscopy in Scalp Seborrheic Dermatitis.

Introduction:Seborrheic dermatitis (SD) is a chronic-recidive inflammatory skin disorder with predilection in areas rich of sebaceous gland. The most common clinical manifestations are pruritus and scales. Although SD can be diagnosed without special tools, other examinations may be needed to determine additional specific therapy. Trichoscopy is one of the noninvasive tools which can help to diagnose SD as it can provide the microstructure view of the scalp.Materials and Methods:This descriptive study was conducted to explore the trichoscopic features of SD and its characteristics. There were 96 SD patients enrolled in this study. The scalp was divided into four areas, and each area was scored based on Seborrheic Area Severity Index, comprising erythema, desquamation, number of papules, and percentage of lesion area. The most severe area was examined with a trichoscopy to observe the characteristics of hair and scalp. The association between trichoscopic findings and SD severity was analyzed with Fisher's exact test.Results:Overall, the participants were 36% males and 64% females with the mean age of 30 (13–70) years old. Based on the trichoscopic examination, the most common findings were thick hair shafts (72%), white scales (69%), arborizing thin vessels (38%), yellowish area (36%), and structureless red area (19%). These findings were not significantly different between mild and moderate SD (P > 0.05).Conclusion:Considering the merits and demerits of trichoscopic examination, it can be helpful to aid the diagnosis of SD. Further studies in Asian population with greater sample size are needed to demonstrate more significant result.

Methodologies for selecting cassava with resistance to dry and black root rot under controlled conditions

ABSTRACT Cassava root rot diseases such as dry and black root rot are listed among the major threats, since its affect the main product (tuberous roots), causing a progressive decline in yield and affecting subsequent crop cycles, being the use of resistant varieties the most reliable control measure on field level. The objective of this study was to identify inoculation methods for the early evaluation of genotypes, considering the level of resistance to dry (DRR) and black (BRR) root rot diseases. Different methodologies and plant tissues were evaluated, based on the immersion of cassava tissues (roots and stem cuttings), soil infestation, and inoculation of detached tissues (leaves, tuberous roots and stem cuttings). The following parameters were evaluated for inoculations based on tissue immersion: disease index (ω); aerial part weight (g); fresh weight of the roots (g); and volume (cm3). For the inoculations on detached tissues, the percentage of lesioned area was determined. Immersion methods for roots and lesioned stems did not show typical symptoms of DRR and BRR during the two-month evaluation period. The soil infestation method did not differ from the stem immersion method as to the reduction of aerial part weight and the disease index, whereas both can be recommended for resistance selection trials. There was a positive correlation between the BRR and DRR data for the stem inoculation (r = 0.94, p = 0.001) and for DRR in the peel and root pulp (r = 0.73, p = 0.05). Therefore, the resistance within each tissue is apparently independent and should be compared with the behavior of the genotypes in the field.

Abstract 227: Megalin Regulates Angiotensinogen and Contributes to Atherosclerosis

Objective: Angiotensinogen (AGT) is the only substrate of the renin-angiotensin system to generate angiotensin peptides, including angiotensin II (AngII), a critical contributor to atherosclerosis. AGT interacts with megalin in proximal convoluted tubules of kidney. The purpose of this study was to determine effects of megalin on AGT, AngII, and atherosclerosis in mice. Methods and Results: Male C57BL/6 mice were injected subcutaneously with vehicle (PBS) or megalin second generation antisense oligonucleotides (ASO) for 5 weeks. Inhibition of megalin was confirmed by more than 80% reduction of megalin mRNA in kidney. Urine was collected using metabolic cages after 5 weeks of vehicle or ASO injections. At termination, blood was collected with EDTA and protease inhibitor cocktail to measure plasma concentrations of renin and AngII, respectively. Urine AGT and renin concentrations were profoundly increased, accompanied by reduction of renal, but not plasma, AngII production. To determine whether megalin inhibition influences atherosclerosis, male LDL receptor -/- mice were injected with vehicle, control ASO, or megalin ASO for 13 weeks. Western diet was started 1 week after the first injection and continued for 12 weeks. Atherosclerosis was quantified by en face analysis of the aortic intimal surface from the ascending aorta to 3 mm proximal to the left subclavian artery branch. Megalin ASO administration led to more than 70% reductions of megalin mRNA in kidney. Consistent with the effects in C57BL/6 mice, AGT concentrations were significantly higher in urine (Vehicle, control ASO and megalin ASO groups: 85 ± 10, 109 ± 71, and 4616 ± 637 ng/ml, respectively; P&lt;0.001 by one way ANOVA with Holm-Sidak method). Plasma total cholesterol concentrations did not differ among groups. Megalin inhibition reduced atherosclerotic lesion area compared to the other two groups (Percent lesion area in Vehicle, control ASO and megalin ASO groups: 23 ± 2, 20 ± 2, 12 ± 1 %, respectively; P &lt; 0.001 by one way ANOVA with Holm-Sidak method). Conclusions: Inhibition of megalin increased urine AGT and renin, reduced renal AngII concentrations, and diminished hypercholesterolemia-induced atherosclerosis in mice.

Impacto do aumento da concentração atmosférica de dióxido de carbono sobre a ferrugem e o crescimento do cafeeiro

Resumo: O objetivo deste trabalho foi avaliar o efeito do aumento da concentração de dióxido de carbono atmosférico sobre o crescimento de plantas e a severidade da ferrugem (causada por Hemileia vastatrix) em cafeeiro (Coffea arabica). Utilizaram-se as cultivares 'Obatã IAC 1669-20' e 'Catuaí Vermelho IAC 144', moderadamente resistente e suscetível à doença, respectivamente. Os tratamentos consistiram de 400 e 508 μmol mol-1 de CO2 atmosférico, em dois tipos de estufas de topo aberto (OTC). As plantas das duas cultivares, cultivadas nas OTCs com adição de CO2, apresentaram aumento de área foliar, e da taxa de crescimento em altura e em diâmetro do caule, em comparação às plantas cultivadas em estufas à concentração ambiente de CO2; porém, as cultivares não diferiram quanto ao teor de cera das folhas. Em 'Catuaí Vermelho IAC 144', a severidade da ferrugem diminuiu com o aumento da concentração de CO2, quanto ao número de lesões, área foliar lesionada, número de lesões esporuladas, área lesionada esporulada, percentagem de área foliar lesionada e área abaixo da curva de progresso da doença; no entanto, em 'Obatã IAC 1669-20', a severidade da doença não variou. A incidência de folhas lesionadas por planta, o período latente, a germinação de urediniósporos e a formação de apressórios não são alterados, à dose de 508 μmol mol-1 de CO2, em ambas as cultivares.

Characterization of recovery, repair, and inflammatory processes following contusion spinal cord injury in old female rats: is age a limitation?

BackgroundAlthough the incidence of spinal cord injury (SCI) is steadily rising in the elderly human population, few studies have investigated the effect of age in rodent models. Here, we investigated the effect of age in female rats on spontaneous recovery and repair after SCI. Young (3 months) and aged (18 months) female rats received a moderate contusion SCI at T9. Behavioral recovery was assessed, and immunohistocemical and stereological analyses performed.ResultsAged rats demonstrated greater locomotor deficits compared to young, beginning at 7 days post-injury (dpi) and lasting through at least 28 dpi. Unbiased stereological analyses revealed a selective increase in percent lesion area and early (2 dpi) apoptotic cell death caudal to the injury epicenter in aged versus young rats. One potential mechanism for these differences in lesion pathogenesis is the inflammatory response; we therefore assessed humoral and cellular innate immune responses. No differences in either acute or chronic serum complement activity, or acute neutrophil infiltration, were observed between age groups. However, the number of microglia/macrophages present at the injury epicenter was increased by 50% in aged animals versus young.ConclusionsThese data suggest that age affects recovery of locomotor function, lesion pathology, and microglia/macrophage response following SCI.

Amlodipine Reduces AngII-Induced Aortic Aneurysms and Atherosclerosis in Hypercholesterolemic Mice

BackgroundThe purpose of this study was to determine effects of amlodipine, a dihydropyridine calcium channel blocker, on development of angiotensin II (AngII)-induced vascular pathologies.Methods and ResultsMale LDL receptor -/- mice were infused with vehicle, amlodipine (5 mg/kg/d), AngII (1,000 ng/kg/min), or AngII + amlodipine for 4 weeks through osmotic pumps (n=10/group). Mice were fed a saturated fat-enriched diet for 1 week prior to pump implantation and during 4 weeks of infusion. Infusion of amlodipine resulted in plasma concentrations of 32 ± 2 ng/ml and 27 ± 2 ng/ml for mice in saline + amlodipine and AngII + amlodipine groups, respectively. This infusion rate of amlodipine did not affect AngII-induced increases in systolic blood pressure. Three of 10 (30%) mice infused with AngII died of aortic rupture, while aortic rupture did not occur in mice co-infused with AngII + amlodipine. Suprarenal aortic width and intimal area of ascending aortas were measured to define aortic aneurysms. In the absence of AngII infusion, amlodipine did not change suprarenal aortic width and ascending aortic area. Infusion of AngII led to profound increases of suprarenal aortic width (saline + vehicle versus AngII + vehicle: 0.86 ± 0.02 versus 1.72 ± 0.26 mm; P=0.0006), whereas co-infusion of AngII and amlodipine diminished abdominal dilation (1.02 ± 0.14 mm; P=0.003). As expected, AngII infusion increased mean intimal area of ascending aortas (saline + vehicle versus AngII + vehicle: 8.5 ± 0.3 versus 12.5 ± 1.1 mm2; P=0.001), while co-infusion of AngII and amlodipine ablated dilation of the ascending aorta (8.6 ± 0.2 mm2; P=0.03). Co-administration of amlodipine also significantly attenuated AngII-induced atherosclerosis in the thoracic region as quantified by percent lesion area (AngII + vehicle versus AngII + amlodipine: 5.8 ± 2.1 % versus 0.3 ± 0.1%; P=0.05).ConclusionsAmlodipine inhibited AngII-induced aortic aneurysms in both the abdominal and ascending regions, and atherosclerosis in hypercholesterolemic mice.

Cardiovascular Changes in Atherosclerotic ApoE-Deficient Mice Exposed to Co60 (γ) Radiation

BackgroundThere is evidence for a role of ionizing radiation in cardiovascular diseases. The goal of this work was to identify changes in oxidative and nitrative stress pathways and the status of the endothelinergic system during progression of atherosclerosis in ApoE-deficient mice after single and repeated exposure to ionizing radiation.Methods and ResultsB6.129P2-ApoE tmlUnc mice on a low-fat diet were acutely exposed (whole body) to Co60 (γ) (single dose 0, 0.5, and 2 Gy) at a dose rate of 36.32 cGy/min, or repeatedly (cumulative dose 0 and 2 Gy) at a dose-rate of 0.1 cGy/min for 5 d/wk, over a period of 4 weeks. Biological endpoints were investigated after 3–6 months of recovery post-radiation. The nitrative stress marker 3-nitrotyrosine and the vasoregulator peptides endothelin-1 and endothelin-3 in plasma were increased (p<0.05) in a dose-dependent manner 3–6 months after acute or chronic exposure to radiation. The oxidative stress marker 8-isoprostane was not affected by radiation, while plasma 8-hydroxydeoxyguanosine and L-3,4-dihydroxyphenylalanine decreased (p<0.05) after treatment. At 2Gy radiation dose, serum cholesterol was increased (p = 0.008) relative to controls. Percent lesion area increased (p = 0.005) with age of animal, but not with radiation treatment.ConclusionsOur observations are consistent with persistent nitrative stress and activation of the endothelinergic system in ApoE−/− mice after low-level ionizing radiation exposures. These mechanisms are known factors in the progression of atherosclerosis and other cardiovascular diseases.

Abstract 352: Adeno-Associated Virus-mediated Restoration of Angiotensinogen Function in Mice With Hepatocyte-specific Deficiency

Background and Objective We have reported previously that genetic or pharmacological inhibition of angiotensinogen (AGT) leads to resistance to dietary fat-induced body weight gain. This phenotype has not been observed in mice subject to pharmacological inhibitors of other components of the renin angiotensin system including renin, ACE, and AT1 receptors. To investigate whether restoration of AGT reverses this lean phenotype, we injected an adeno-associated virus (AAV) 2/8 vector carrying wild type AGT to mice with hepatocyte-specific deficiency of AGT (hepAGT -/-). Methods and Results HepAGT -/- mice were generated by disrupting AGT gene in hepatocytes via albumin promoter driven Cre recombinase expressed in mice with floxed AGT alleles. An AAV AGT vector was constructed with the insertion of wild type AGT. AAV null vector was used as control. AAV expression was driven by hepatocyte-specific thyroxine-binding globulin promoter. Five groups of male LDL receptor -/- mice at age of 8 - 10 weeks were studied: wild type (hepAGT +/+) mice received either no AAV (PBS) or null AAV, and hepAGT -/- mice received low dose (1 x 1010 genome copy), high dose (3 x 1010 genome copy), or null AAV. Four weeks after AAV injection (i.p.), all mice were fed a saturated fat-enriched diet (42% calories from milk fat) for 12 weeks. Plasma samples were collected through retro-orbital bleeding at weeks 2, 4, 8, and 16 after AAV injection. Plasma AGT concentrations peaked between weeks 2 and 4, then declined modestly, irrespective of dosage. However, at the high dose, plasma AGT concentrations in hepAGT -/- mice were comparable to those in hepAGT +/+ mice. Plasma total cholesterol concentrations, body weight gains, and systolic blood pressures were not different between hepAGT +/+ and hepAGT -/- mice receiving either dose of AGT AAV. Atherosclerosis, quantified as percent lesion area covering the intima of the aortic arch, was equivalent between hepAGT -/- mice receiving either dose of AGT AAV and hepAGT +/+ mice, whereas it was nearly absent in hepAGT -/- mice receiving null AAV. Conclusions AGT in an AAV 2/8 vector efficiently recovers plasma AGT concentration in hepAGT -/- mice in a dose-dependent manner. This approach permits the elucidation of structural mutations on AGT function.

Gastroprotective activity of the ethanol extract from the inner bark of Caesalpinia pyramidalis in rats

Ethnopharmacological relevanceCaesalpinia pyramidalis Tul. (Fabaceae), known as “catingueira”, has been used in folk medicine in the treatment of various disorders such as gastritis, heartburn, indigestion, and stomach ache. However, the gastroprotective properties of this species have not yet been studied. Materials and methodsThe ethanol extract of Caesalpinia pyramidalis inner bark was used in rats via oral route, at the doses of 30, 100, and 300mg/kg. The antiulcer assays were performed using the ethanol- and nonsteroidal anti-inflammatory drug-induced ulcer models. Gastric secretion parameters (volume, pH, and total acidity) were also evaluated by the pylorus ligated model, and the mucus in the gastric content was determined. The anti-Helicobacter pylori activity of the ethanol extract of Caesalpinia pyramidalis was performed using the agar-well diffusion and broth microdilution methods. ResultsThe ethanol extract (30, 100, and 300mg/kg) produced dose dependent inhibition (P<0.01) on the ulcer lesion index, the total lesion area, and the percentage of lesion area in the ethanol-induced ulcer model. The ethanol extract (30, 100, and 300mg/kg) also reduced (P<0.001) the ulcer index in the indomethacin-induced ulcer model. In the model ligature pylorus, the treatment with Caesalpinia pyramidalis ethanol extract failed to significantly change the gastric secretion parameters. However, after treatment with the ethanol extract of Caesalpinia pyramidalis (30, 100, and 300mg/kg), there was a significant increase (P<0.05) in mucus production. The ethanol extract showed anti-Helicobacter pylori activity, with inhibition halos of 12.0±1.7mm at 10,000μg/mL. The minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values of the ethanol extract were of 625 and 10,000μg/mL, respectively. ConclusionsCollectively, the present results suggest that the ethanol extract of Caesalpinia pyramidalis displays gastroprotective actions, supporting the folkloric usage of the plant to treat various gastrointestinal disturbances.

Visual and Electronic Evaluations of Detached Strawberry Leaves Inoculated with Colletotrichum Species

Inoculation of detached strawberry leaves with Colletotrichum species may provide an accurate, rapid, non-destructive method of identifying anthracnose resistant germplasm. Two assessments of anthracnose disease severity were compared on detached strawberry leaves inoculated with Colletotrichum fragariae and C. gloeosporioides: a quantitative assessment made via computer-based image analysis and a visual assessment made by two independent raters. The image analysis provided a precise measurement of percent lesion area of infected leaves. There was a strong positive correlation between percent lesion area and the visual disease scores of the raters.

Hyaluronan Anchored to Activated CD44 on Central Nervous System Vascular Endothelial Cells Promotes Lymphocyte Extravasation in Experimental Autoimmune Encephalomyelitis

The extravasation of lymphocytes across central nervous system (CNS) vascular endothelium is a key step in inflammatory demyelinating diseases including multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). The glycosaminoglycan hyaluronan (HA) and its receptor, CD44, have been implicated in this process but their precise roles are unclear. We find that CD44(-/-) mice have a delayed onset of EAE compared with wild type animals. Using an in vitro lymphocyte rolling assay, we find that fewer slow rolling (<1 μm/s) wild type (WT) activated lymphocytes interact with CD44(-/-) brain vascular endothelial cells (ECs) than with WT ECs. We also find that CD44(-/-) ECs fail to anchor HA to their surfaces, and that slow rolling lymphocyte interactions with WT ECs are inhibited when the ECs are treated with a pegylated form of the PH20 hyaluronidase (PEG-PH20). Subcutaneous injection of PEG-PH20 delays the onset of EAE symptoms by ~1 day and transiently ameliorates symptoms for 2 days following disease onset. These improved symptoms correspond histologically to degradation of HA in the lumen of CNS blood vessels, decreased demyelination, and impaired CD4(+) T-cell extravasation. Collectively these data suggest that HA tethered to CD44 on CNS ECs is critical for the extravasation of activated T cells into the CNS providing new insight into the mechanisms promoting inflammatory demyelinating disease.

Infectivity and sporulation potential of Phytophthora kernoviae to select North American native plants

Phytophthora kernoviae exhibits comparable epidemiology to Phytophthora ramorum in invaded UK woodlands. Because both pathogens have an overlapping geographic range in the UK and often concurrently invade the same site, it is speculated that P. kernoviae may also invade North American (NA) forests threatened by P. ramorum, the cause of Sudden Oak Death. This paper addresses the susceptibility of select NA plants to P. kernoviae, including measures of disease incidence and severity on wounded and unwounded foliage. The potential for pathogen transmission and survival was investigated by assessing sporangia and oospore production in infected tissues. Detached leaves of Rhododendron macrophyllum, Rhododendron occidentale and Umbellularia californica, and excised roots of U. californica and R. occidentale were inoculated with P. kernoviae and percent lesion area was determined after 6 days. Leaves were then surface sterilized and misted to stimulate sporulation and after 24 h sporangia production was assessed. The incidence of symptomless infections and sporulation were recorded. All NA native plants tested were susceptible to P. kernoviae and supported sporangia production; roots of U. californica and R. occidentale were both susceptible to P. kernoviae and supported sporangia production. Oospore production was also observed in U. californica roots. The results highlight the vulnerability of select NA native plants to infection by P. kernoviae, suggest that symptomless infections may thwart pathogen detection, and underscore the importance of implementing a proactive and adaptive biosecurity plan.

Oxytocin Attenuates Atherosclerosis and Adipose Tissue Inflammation in Socially Isolated ApoE−/− Mice

To determine the effect of exogenous oxytocin (OT) administration on inflammation and atherosclerosis in socially isolated apoE(-/-) mice. Hyperlipidemic animals housed in isolated or stressful social environments display more extensive atherosclerosis than those in an affiliative social environment. The neurohypophyseal peptide OT may be involved in both affiliative social behavior and cardiovascular homeostasis, suggesting a role in mediating the benefits of positive social interactions on atherosclerosis. A total of 43, 12-week-old, apoE(-/-) mice were surgically implanted with osmotic minipumps containing OT (n = 23) or vehicle (n = 20). Blood samples were taken at baseline and after 6 weeks and 12 weeks of treatment. After 12 weeks of treatment, animals were killed, and samples of adipose tissue were dissected from a subset of OT-treated (n = 12) and vehicle-treated (n = 12) animals and incubated in culture media for 6 hours. Media samples were analyzed for interleukin (IL)-6 concentration corrected by sample dry weight. Aortas were dissected, formalin-fixed, and stained with oil-red O for en face quantification of lesion area. t tests were used to compare group means on measures of percent lesion area and IL-6 concentrations. There were no group differences in plasma lipids. Adipose tissue samples taken from OT-treated animals secreted significantly less IL-6 over 6 hours (p < .01). OT-treated animals displayed significantly less atherosclerosis in the thoracic aorta (p < .05). These results indicate that peripheral OT administration can inhibit atherosclerotic lesion development and adipose tissue inflammation, suggesting a potential role for this neuropeptide in mediating the benefits of stable group housing on atherosclerosis.