Relationship between total ghrelin and inflammation in hemodialysis patients

In hemodialysis (HD) patients studies have shown that plasma ghrelin is increased and it has been speculated that ghrelin levels might be related to systemic inflammation. The present study attempted to correlate the serum levels of total ghrelin with serum TNF-α and IL-6, and with nutritional status and body composition in HD patients. Forty-seven HD patients from a single dialysis unit (18 women, mean age 55.3 ± 12.2 yr; BMI 24.4 ± 4.2 kg/m²; % body fat 29.4 ± 7.4%) were studied and compared to 21 healthy subjects (12 women, 50.7 ± 15.7 yr and BMI 25.6 ± 4.0 kg/m²; % body fat 30.0 ± 5.7%). Biochemical data, serum total ghrelin, TNF-α and IL-6 levels were measured. The body composition was evaluated by dual energy X-ray absortiometry (DEXA) and energy and protein intake were evaluated. Patients showed elevated plasma ghrelin levels when compared to healthy subjects (1.14 ± 1.0 ng/mL vs 0.58 ± 0.4; p < 0.001). There was a positive correlation between ghrelin levels and TNF-α (r = 0.25; p < 0.04), IL-6 (r = 0.42; p < 0.02), and a negative correlation between TNF-α and protein intake (r = −0.28; p < 0.03), and energy intake (r = −0.34; p < 0.01). No correlation was observed with any aspect of body composition. Plasma ghrelin levels are elevated in HD patients and associated with the state of systemic inflammation. We suggest that the inflammatory state may affect ghrelin bioactivity and metabolism in hemodialysis patients.     

Factors controlling vegetation structure in peatland lakes—Two conceptual models of plant zonation

Two conceptual models of plant zonation in peatland lakes are given. The first represents vegetation on slightly sloping substrate (N < 0.2) in shallow and relatively large lakes. The vegetation is not diverse (H′ = 0.0 ± 0.01). The frequency and biomass of the dominant (Sphagnum denticulatum) correlate positively with lake size, and negatively with depth and substrate slope. They are also correlated with water transparency and water color (r = −0.53), concentrations of total organic carbon (r = −0.43), Ca²⁺ (r = 0.40) and humic acids (r = −0.46), and redox potential (r = 0.44). The second model represents vegetation on steep peat walls (N > 0.3) in deep, usually small lakes. Plants occur only on the upper part of the peat wall or form a multispecies curtain hanging from the lip of peat at the top. Species diversity in this scenario is higher (H′ = 0.18 ± 0.17). The curtains usually are composed of mosses such as Warnstorfia exannulata, S. cuspidatum and S. riparium, and vascular plants are rare. The frequency and biomass of bryophytes in this type of structure are related to substrate slope (r = 0.56), lake depth (r = 0.56), Ca²⁺ concentration (r = −0.69) and water color (r = −0.51). In both models, plant biomass is correlated with temperature (r = −0.78), irradiance (r = −0.64) and water oxygenation (r = −0.54).     

Urinary free cortisone, but not cortisol, is associated with urine volume in severe obesity

Background

High urine volume enhances urinary free cortisol (UFF) and cortisone (UFE) excretion rates in normal-weight adults and children. Renal excretion rates of glucocorticoids (GC) and their metabolites are frequently altered in obesity. The aim of the present study was to investigate whether UFF and UFE excretion is also affected by urine volume in severely obese subjects.

Experimental

In 24-h urine samples of 59 extremely obese subjects (mean BMI 45.3 ± 8.9 kg/m²) and 20 healthy lean subjects (BMI 22.1 ± 1.8 kg/m²), UFF and UFE, tetrahydrocortisol (THF), 5α-tetrahydrocortisol (5α-THF), and tetrahydrocortisone (THE) were quantified by RIA. The sum of THF, 5α-THF, and THE (GC3), the three major GC metabolites, reflects daily cortisol secretion. 11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity was assessed by the ratio UFE/UFF. Daily GC excretion rates were corrected for urine creatinine and adjusted for gender and body weight.

Results

In extremely obese subjects, urine volume was significantly associated with creatinine-corrected UFE and 11β-HSD2 activity after adjustment for gender and BMI (r = 0.47, p = 0.0002 and r = 0.31, p = 0.02, respectively). However, urine volume was not associated with creatinine-corrected UFF and GC3 (p = 0.4 and p = 0.6, respectively). In lean controls, urine volume was significantly associated with creatinine-corrected UFE and UFF (r = 0.58, p = 0.01 and r = 0.55, p = 0.02, respectively), whereas urine volume was not associated with 11β-HSD2 activity after appropriate adjustment (p = 0.3).

Conclusions

In severe obesity, in contrast to normal weight, renal excretion of UFE, but not of UFF is affected by fluid intake. This discrepancy may be due to the increased renal 11β-HSD2 activity in obesity.     

In vivo passages of heterologous Beauveria bassiana isolates improve conidial surface properties and pathogenicity to Nilaparvata lugens (Homoptera: Delphacidae)

In entomopathogenic hyphomycetes, desired candidates against the brown planthopper, Nilaparvata lugens (a sap-sucking rice pest in Asia), are lacking. In this study, 21 Beauveria bassiana isolates from heterologous host insects showed low pathogenicity to third-instar nymphs sprayed at the high concentration of ∼1000 conidia/mm², causing only 2-23% mortalities. Of those, three isolates killed significantly more nymphs (up to 45-62%) after two in vivo passages but no more after further passage. Conidial hydrophobicity rates (H_r), zeta potentials (P_z), and subtilisin-like protease (Pr1) activities (A_p) of these isolates showed the same trends in the three host passages (N: 0-3). In multivariate correlation, the variables N, H_r and P_z were found contributing 89% to the mortality variation (r² = 0.89). Significant positive correlations were also found between H_r and N (r² = 0.64), P_z and N (r² = 0.52), A_p and N (r² = 0.51), H_r and A_p (r² = 0.45), and P_z and A_p (r² = 0.57), respectively. However, irregular changes of H_r and P_z occurred in four other isolates, whose pathogenicity to N. lugens was not enhanced by repeated host passages, resulting in no correlation between the variables. Our data indicate that the conidial surface properties H_r and P_z associated with cuticle adhesion reflect the heterologous host-induced adaptation and help to select fungal candidates against N. lugens from repeated in vivo passages.     

Rosiglitazone transiently disturbs calcium homeostasis in monocytic cells

The PPARγ agonist Rosiglitazone exerts anti-hyperglycaemic effects by regulating the long-term expression of genes involved in metabolism, differentiation and inflammation. In the present study, Rosiglitazone treatment rapidly inhibited (5-30 min) the ER Ca²⁺ ATPase SERCA2b in monocytic cells (IC₅₀ = 1.88 μM; p < 0.05), thereby disrupting short-term Ca²⁺ homeostasis (resting [Ca²⁺]_cyto = 121.2 ± 2.9% basal within 1 h; p < 0.05). However, extended Rosiglitazone treatment (72 h) induced dose-dependent SERCA2b up-regulation, and restored calcium homeostasis, in monocytic cells (SERCA2b mRNA: 138.7 ± 5.7% basal (1 μM)/215.0 ± 30.9% basal (10 μM); resting [Ca²⁺]_cyto = 97.3 ± 8.3% basal (10 μM)). As unfavourable cardiovascular outcomes, possibly related to disrupted cellular Ca²⁺ homeostasis, have been linked to Rosiglitazone, this effect may be of clinical interest. In contrast, in PPRE-luciferase reporter-gene assays, Rosiglitazone induced non-dose-dependent PPARγ-dependent effects (1 μM: 152.5 ± 4.9% basal; 10 μM: 136.1 ± 5.1% basal (p < 0.05 for 1 μM vs. 10 μM)). Thus, we conclude that Rosiglitazone can exert PPARγ-independent non-genomic effects, such as the SERCA2b inhibition seen here, but that long-term Rosiglitazone treatment did not perturb resting [Ca]_cyto in this study.     

Association of the Ser326Cys polymorphism in the OGG1 gene with type 2 DM

The association of the Ser326Cys polymorphism of the 8-oxoguanine glycosylase 1 (OGG1) gene with type 2 diabetes was examined using a Japanese population (n (M/W): 4585 (2085/2500); age: 62.6 ± 10.9 years). HbA1c levels and frequency of diabetic subjects were significantly higher in subjects with genotypes with Cys allele than in those without (p = 0.032 and 0.037, respectively). Multiple logistic regression analysis showed that genotypes with Cys allele were significantly associated with diabetes (OR: 1.32, p = 0.0289). In subjects whose glucose tolerance was classified by FPG and 2-h PG (n = 1.634), the association was more substantial (genotypes with Cys allele vs. without, OR: 1.70, p = 0.0059; genotypes Cys/Cys vs. Ser/Ser, OR: 2.19, p = 0.0008). In subjects with genotype Ser/Ser, the insulin secretion index, HOMA-β, increased in the subjects with glucose intolerance and decreased in the subjects with diabetes, while, in subjects with genotypes Ser/Cys + Cys/Cys, HOMA-β decreased as the glucose tolerance progressed (p for trend = 0.010).     

Regional variation in adipogenesis and IGF regulatory proteins in the fetal baboon

Intrauterine growth rate is associated with body distribution in adulthood suggesting differential response of fetal fat depots to nutritional modifications. We hypothesize that there is regional differences in fetal adipogenesis, in part, due to depot-specific regulation of the availability of insulin growth factors. In near-term baboon fetuses (n = 3-5), the subcutaneous abdominal vs. omental preadipocytes had (1) more extensive lipid accumulation as assessed by BODIPY (lipid staining) to DAPI (nuclei) absorbance ratios (mean ± SEM; 0.51 ± 0.21, 0.35 ± 0.09, p < 0.05), (2) lower (p < 0.05) secretion of IGF-binding protein 4 (9.6 ± 1.2 vs. 17.4 ± 2.8 ng/ml) and its protease pregnancy associated plasma protein A (24.6 ± 1.9 vs. 39.1 ± 6.3 μIU/ml), (3) lower protein expression of IGF2 “clearance” receptor in cell lysate (0.28 ± 0.03 vs. 0.53 ± 0.02 OD U/mm², p < 0.05); all variables were intermediate in femoral preadipocytes. The regional variation of the adipogenesis and the IGF regulatory pathway set the stage for differential responsiveness of fat depots to external signals.     

Allergen-specific B cell subset responses in cow’s milk allergy of late eczematous reactions in atopic dermatitis

B cells have regulatory functions in immune responses. Antigen-specific responses of B cell subsets by allergen stimulation ex vivo were examined in milk allergy of late eczematous reactions. Eight milk allergy subjects and 13 milk tolerant subjects were selected by DBPCFC. PBMCs were stimulated by casein ex vivo and stained for B cell subsets using monoclonal antibodies. CD19+ B cells unchanged from 8.7 ± 3.8% to 8.0 ± 5.1% (p = 0.504, n = 8) in the milk allergy group and decreased in the milk tolerant group from 8.5 ± 3.2% to 5.0 ± 1.6% (p = 0.001, n = 13). The fraction of apoptotic B cells in B cells significantly decreased 4.4 ± 3.1% to 1.3 ± 0.4% (p = 0.027, n = 4) in the allergy group and insignificantly increased from 2.8 ± 0.6% to 5.4 ± 2.6% (p = 0.059, n = 6) in the milk tolerant group. CD5+ regulatory B1 cell% in B cells decreased in milk allergy subjects from 36.2 ± 5.0% to 31.0 ± 5.7% (p = 0.010) and unchanged in milk tolerant subjects from 41.6 ± 10.2% to 43.8 ± 10.0% (p = 0.413). IL-10 producing CD19+CD5+ regulatory B cell% in CD19+CD5+ regulatory B cells significantly decreased from 24.9 ± 6.5% to 13.8 ± 5.6% (p = 0.002, n = 5) by casein stimulation in milk allergy group and unchanged from 44.8 ± 11.3% to 43.9 ± 10.0% (p = 0.297, n = 5) in the milk tolerant group. B cell subset responses to IL-4 and IL-5 were also similar in both groups. B cell subset changes seemed to have diagnostic value. Exact immunologic roles of regulatory CD5+ B1 cells need further investigation.     

Effects of treatment with a prostaglandin analogue on developmental dynamics and functionality of induced corpora lutea in goats

The aim of this study was to compare morphological and functional features of spontaneous and induced corpora lutea (CLs) in goats. Fourteen adult and cycling Anglo Nubian goats (Argentina) were randomly allocated to two groups: Group N (n = 7) included goats with natural spontaneous oestrus and Group PG (n = 7) included does in which oestrus was synchronized by the administration of two i.m. cloprostenol doses, 10 days apart. In both groups, oestrous behaviour was checked twice daily (Day of oestrus = Day 0) and daily transrectal ultrasonographies were performed for evaluating CLs and follicles dynamics through the complete subsequent oestrous cycle; the luteal activity was determined directly, in terms of progesterone (P4) secretion, and indirectly, by assessing effects of CL on follicular dynamics. All goats exhibited oestrous behaviour and ovulation without differences in ovulation rate (N: 1.67 ± 0.2, PG: 2.0 ± 0.1). The total luteal tissue area showed linear growth from Day 4 to Day 15 of oestrous cycle in all goats, but the developmental dynamics differed between groups, treated goats had larger area (P < 0.01). Plasma P4 concentrations also increased from Day 0 to Day 15 in all the does; however, from Day 5 to Day 15, treated does had a lower concentrations than the untreated group (P < 0.001). There were differences in the development of follicular waves between groups; assessment of size-distribution showed that treated group had a higher number of small and larger follicles (P < 0.05). The largest follicles recorded in treated goats had a higher maximum diameter both at the first (PG: 7.6 ± 0.8 mm; N: 4.9 ± 0.7 mm, P < 0.05) and second follicular waves (PG: 6.3 ± 1.4 mm; N: 5.0 ± 0.4 mm, P < 0.05) and a longer growth phase during the second wave (PG: 6.5 ± 1.7 days; N: 4.6 ± 0.7 days, P < 0.05), coincident with the period of maximal luteal secretion. In conclusion, synchronization of oestrus and ovulation by the administration of a prostaglandin analogue causes differences in developmental dynamics and functionality of induced corpora lutea when compared to natural spontaneous ovulation.     

Biotic and abiotic regulation of resting spore formation in vivo of obligate aphid pathogen Pandora nouryi: Modeling analysis and biological implication

Entomophthoralean fungus Pandora nouryi is an obligate aphid pathogen that enables to produce resting spores (azygospores) for surviving host absence. To explore possible mechanisms involved in the regulation of resting spore formation in vivo, host cohorts consisting of 40-60 nymphs of green peach aphid Myzus persicae produced within 24 h on cabbage leaf discs in petri dishes were exposed to spore showers of P. nouryi at the concentrations (C) from a very few to nearly 2000 conidia/mm² and then reared for 7-11 days at the regimes of 10-25 °C (T) and 8-16 h daylight (H_L) or ambient (17.5 ± 3.1 °C, 13:11 L:D). Aphid mortalities observed from 35-83 cohorts (showered separately) at each regime showed typical sigmoid trend and fit well a general logistic equation (0.79 ? r² ? 0.88), yielding similar LC₅₀ estimates of 1.7-6.1 conidia/mm². The proportions (P) of cadavers forming resting spores in the cohorts also fit the same equation (0.73 ? r² ? 0.85) at all tested regimes except at 10 °C, a low temperature for the host-pathogen interaction. This indicates the dependence of resting spore formation on the spore concentration. The effects of T and H_L on P over C were well elucidated by the fitted modified logistic equations P = 0.578/{1 + exp[1.710 − (0.136 − 0.0053T)C]} and P = 0.534/{1 + exp[1.639 + (0.034 − 0.0053H_L)C]} (both r² = 0.79). Our results highlight that the resting spore formation in vivo of P. nouryi is regulated primarily by the concentration of host-infecting conidia discharged from cadavers and facilitated by lower temperature and longer daylight.     

Leptin and leptin receptor genetic variants associate with habitual physical activity and the arm body composition response to resistance training

Purpose

We investigated the influence of Leptin (LEP) and leptin receptor (LEPR) SNPs on habitual physical activity (PA) and body composition response to a unilateral, upper body resistance training (RT) program.

Methods

European-derived American volunteers (men = 111, women = 131, 23.4 ± 5.4 yr, 24.4 ± 4.6 kg·m^− 2) were genotyped for LEP 19 G>A (rs2167270), and LEPR 326 A>G (rs1137100), 668 A>G (rs1137101), 3057 G>A (rs1805096), and 1968 G>C (rs8179183). They completed the Paffenbarger PA Questionnaire. Arm muscle and subcutaneous fat volumes were measured before and after 12 wk of supervised RT with MRI. Multivariate and repeated measures ANCOVA tested differences among phenotypes by genotype and gender with age and body mass index as covariates.

Results

Adults with the LEP 19 GG genotype reported more kcal/wk in vigorous intensity PA (1273.3 ± 176.8, p = 0.017) and sports/recreation (1922.8 ± 226.0, p < 0.04) than A allele carriers (718.0 ± 147.2, 1328.6 ± 188.2, respectively). Those with the LEP 19 GG genotype spent more h/wk in light intensity PA (39.7 ± 1.6) than A allele carriers (35.0 ± 1.4, p = 0.03). In response to RT, adults with the LEPR 668 G allele gained greater arm muscle volume (67,687.05 ± 3186.7 vs. 52,321.87 ± 5125.05 mm³, p = 0.01) and subcutaneous fat volume (10,599.89 ± 3683.57 vs. − 5224.73 ± 5923.98 mm³, p = 0.02) than adults with the LEPR 668 AA genotype, respectively.

Conclusion

LEP19 G>A and LEPR 668 A>G associated with habitual PA and the body composition response to RT. These LEP and LEPR SNPs are located in coding exons likely influencing LEP and LEPR function. Further investigation is needed to confirm our findings and establish mechanisms for LEP and LEPR genotype and PA and body composition associations we observed.     

Complexation of curium(III) by adenosine 5′-triphosphate (ATP): A time-resolved laser-induced fluorescence spectroscopy (TRLFS) study

The complex formation of curium(III) with adenosine 5′-triphosphate (ATP) was determined by time-resolved laser-induced fluorescence spectroscopy (TRLFS). The interaction between soluble species of curium(III) with ATP was studied at trace Cm(III) concentrations (3 × 10⁻⁷ M). The concentrations of ATP were varied between 6.0 × 10⁻⁷ and 1.5 × 10⁻⁴ M in the pH range of 1.5-7.0 using 0.154 M NaCl as background electrolyte.Three Cm-ATP species, M_pH_qL_r, could be identified from the fluorescence emission spectra: (i) CmH₂ATP⁺ with a peak maximum at 598.6 nm, (ii) CmHATP with a peak maximum at 600.3 nm, and (iii) CmATP⁻ with a peak maximum at 601.0 nm. The formation constants of these complexes were calculated from TRLFS measurements to be log β₁₂₁ = 16.86 ± 0.09, log β₁₁₁ = 13.23 ± 0.10, and log β₁₀₁ = 8.19 ± 0.16. The hydrated Cm-ATP species showed fluorescence lifetimes between 88 and 96 μs; whereas the CmATP⁻ complex has a significantly longer fluorescence lifetime of 187 ± 7 μs.     

Parnassius apollo last-instar larvae development prediction by analysis of weather condition as a tool in the species’ conservation

Parnassius apollo (Lepidoptera: Papilionidae) has already disappeared or is under threat of extinction in many of its former habitats. It has been documented that weather conditions – anomalies in particular – contributed to this process. In this study, we combined developmental data obtained previously for the last-instar Apollo larvae (collected in 1996, 1997, and 2003) with corresponding meteorological data to assess the effects of ambient temperature and rainfall episodes on the duration and the completion of the instar. For comparing the temperature effect, we applied the degree-day concept. We found significant positive correlation between the number of rainy days during the instar development (x) and its duration time (y): y = 8.293 + 0.936x (± 2.813) (r = 0.662, P < 10⁻⁷). Logarithmic transformation of the growth curves of the last-instar Apollo larvae revealed that there was no difference in growth among females; however, there was slower growth of males in 2003 in comparison to 1996. Growth (y) of female Apollo larvae as a function of instar duration (x) can by described by one common equation, irrespectively of the year: y = 317.6 + 502.3 lnx (± 263.3) (r = 0.82, P < 10⁻⁴).     

Characterisation of allergen-specific responses of IL-10-producing regulatory B cells (Br1) in Cow Milk Allergy

CD19+CD5+ regulatory B cells regulate immune responses by producing IL-10. IL-10-producing regulatory B cell (Br1) responses by allergen stimulation were investigated in human food allergy. Six milk allergy patients and eight milk-tolerant subjects were selected according to DBPCFC. PBMCs were stimulated by casein in vitro and stained for intracellular IL-10 and apoptosis. In response to allergen stimulation, Br1 decreased from 26.2 ± 18.3 to 15.5 ± 8.9% (p = 0.031, n = 6) in the milk allergy group and increased from 15.4 ± 9.0 to 23.7 ± 11.2% (p = 0.023, n = 8) in the milk-tolerant group. Apoptotic non-IL-10-producing regulatory B cells increased from 21.8 ± 9.3 to 38.0 ± 16.1% (p = 0.031, n = 6) in the milk allergy group and unchanged from 28.8 ± 13.8 to 28.0 ± 15.0% (p = 0.844, n = 8) in the milk-tolerant group. Br1 may be involved in the immune tolerance of food allergies by producing IL-10 and simultaneously undergoing apoptosis in humans. The exact roles for Br1 in immune tolerance needs to be further investigated.     

N:P ratios, δN fractionation and nutrient resorption along a nitrogen to phosphorus limitation gradient in an oligotrophic wetland complex

The vegetation N:P ratio is thought to be a diagnostic indicator of the nature of nutrient limitation in wetland vegetation. It should therefore be closely linked to other indicators of nutrient acquisition and conservation, such as nitrogen stable isotope fractionation (δ¹⁵N), nutrient resorption efficiency (RE) and resorption proficiency (RP). However, the interrelationships among these traits and the N:P ratio remain unclear. We compared tissue nutrient concentrations, N:P ratios, δ¹⁵N fractionation, RE, and RP along an N to P limitation gradient in an oligotrophic wetland valley in the South Island of New Zealand. Within the valley, the soil TN:TP ratio increased from 1.3 to 18.0 in three discrete wetlands along the gradient. In pooled data from all vegetation communities within each site, the mass-based vegetation N:P ratio correlated significantly (r² = 0.35, P < 0.01) to soil TN:TP ratios and increased from 10.2 ± 2.7 to 13.5 ± 3.6 along the N to P limitation gradient. This was accompanied by an increase in tissue δ¹⁵N enrichment from 2.05 ± 1.12‰ to 6.27 ± 1.70‰, consistent with more open N cycling and lower N demand. These trends held within all vegetation types, but were particularly strong in a Typha orientalis (C-strategist) community (soil TN:TP vs vegetation N:P correlation r² = 0.78, P < 0.001; δ¹⁵N increase from 1.81 ± 0.44‰ to 7.73 ± 1.79‰). The individual N and P concentrations and retention patterns were more species-specific and less responsive to the nutrient limitation gradient. T. orientalis maximised N resorption as N limitation increased (increasing NRE from 50.8 ± 3.3% to 71.7 ± 7.4%; reducing NRP from 0.70 ± 0.12% to 0.36 ± 0.13%) but did not alter PRE or PRP, whereas the S-strategist Schoenus pauciflorus maximised P resorption as P limitation increased (increasing PRE from 48.0 ± 5.6% to 73.5 ± 10.1%; reducing PRP from 0.053 ± 0.008% to 0.015 ± 0.004%) but did not alter NRE or NRP. These results show that the tissue N:P ratio and its associated δ¹⁵N enrichment are highly responsive indicators of the relative availability of N and P at the site and community level. However, they are not indicators of species-specific physiological requirements for N and P, or of likely responses of individual species to N or P enrichment, which are better interpreted from indicators such as RE and RP that describe nutrient retention behaviour.     

Nitric oxide diffusion rate is reduced in the aortic wall

Endogenous nitric oxide (NO) plays important physiological roles in the body. As a small diatomic molecule, NO has been assumed to freely diffuse in tissues with a diffusion rate similar to that in water. However, this assumption has not been tested experimentally. In this study, a modified Clark-type NO electrode attached with a customized aorta holder was used to directly measure the flux of NO diffusion across the aortic wall at 37°C. Experiments were carefully designed for accurate measurements of the apparent NO diffusion coefficient D and the partition coefficient α in the aortic wall. A mathematical model was presented for analyzing experimental data. It was determined that α = 1.15 ± 0.11 and D = 848 ± 45 μm²/s (n = 12). The NO diffusion coefficient in the aortic wall is nearly fourfold smaller than the reported diffusion coefficient in solution at 37°C, indicating that NO diffusion in the vascular wall is no longer free, but markedly dependent on the environment in the tissue where these NO molecules are. These results imply that the NO diffusion rate in the vascular wall may be upregulated and downregulated by certain physiological and/or pathophysiological processes affecting the composition of tissues.     

Decolorization of malachite green by cytochrome c in the mitochondria of the fungus Cunninghamella elegans

We studied the decolorization of malachite green (MG) by the fungus Cunninghamella elegans. The mitochondrial activity for MG reduction was increased with a simultaneous increase of a 9-kDa protein, called CeCyt. The presence of cytochrome c in CeCyt protein was determined by optical absorbance spectroscopy with an extinction coefficient (E_550-535) of 19.7 ± 6.3 mM⁻¹ cm⁻¹ and reduction potential of + 261 mV. When purified CeCyt was added into the mitochondria, the specific activity of CeCyt reached 440 ± 122 μmol min⁻¹ mg⁻¹ protein. The inhibition of MG reduction by stigmatellin, but not by antimycin A, indicated a possible linkage of CeCyt activity to the Qo site of the bc1 complex. The RT-PCR results showed tight regulation of the cecyt gene expression by reactive oxygen species. We suggest that CeCyt acts as a protein reductant for MG under oxidative stress in a stationary or secondary growth stage of this fungus.     

Quercetin glucosides promote ischemia-induced angiogenesis,but do not promote tumor growth

Aims

Dietary flavonoid intake shows a significant inverse association with mortality from coronary heart disease, incidence of myocardial infarction and stroke. Quercetin is one of the most common flavonoids in our diet and has several favorable biological activities. Quercetin glucosides, which are enzymatically trans-glycosylated isoquercitrin, have high water-solubility and bioavailability compared with quercetin. Here, we investigated the effects of quercetin glucosides on collateral development in a murine hindlimb ischemia model.

Main methods

We induced hindlimb ischemia in 24- to 32-week-old male C3H/HeJ mice by resecting the right femoral artery. Then, 0.5% carboxymethyl cellulose (control) or quercetin glucosides (100 mg/kg/day) were administered daily by gavage. Blood flow was monitored weekly by laser Doppler imaging.

Key findings

Recovery of blood flow to the ischemic leg was significantly enhanced by quercetin glucosides (blood flow ratio at 4 weeks: control, 0.57 ± 0.11; quercetin glucosides, 0.95 ± 0.10, p < 0.05). Furthermore, anti-CD31 immunostaining revealed that quercetin glucosides increased capillary density in the ischemic muscle (control, 200 ± 24/mm²; quercetin glucosides, 364 ± 41/mm², p < 0.01). Quercetin glucosides did not promote tumor growth. The beneficial effect of quercetin glucosides was abrogated in eNOS-deficient mice.

Significance

These results suggest that quercetin glucosides may have therapeutic potential to promote angiogenesis in ischemic tissue.