The relationship of nitric oxide synthesis capacity,oxidative stress,and albumin-to-creatinine ratio in black and white men: the SABPA study

Inadequate substrate availability and increased nitric oxide synthase inhibitor levels attenuate nitric oxide (NO) synthesis, whereas increased vascular oxidative stress may lead to inactivation of NO. We compared markers of NO synthesis capacity and oxidative stress in a bi-ethnic male population. Inter-relationships of ambulatory blood pressure and urinary albumin-to-creatinine ratio with NO synthesis capacity and oxidative stress markers were investigated. NO synthesis capacity markers (L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA)) and oxidative stress markers (serum peroxides, total glutathione, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase) were measured. Black men displayed higher blood pressure and albumin-to-creatinine ratio (all p < 0.001), while NO synthesis capacity was more favorable (higher L-arginine and lower ADMA (p ≤ 0.003)). Antioxidant enzyme activities were similar except for the redox status markers (GR activity and GR/GPx ratio), which were upregulated in black men (p < 0.001). In black men, ADMA was inversely related to GPx activity (R ² = 0.15; β = ?0.20; p = 0.050) and GPx/SOD ratio (R ² = 0.24; β = ?0.37; p < 0.001), but none of these markers related to blood pressure or albumin-to-creatinine ratio. In white men, albumin-to-creatinine ratio was positively associated with ADMA (R ² = 0.18; β = 0.39; p < 0.001) while ADMA was inversely related to GR activity (R ² = 0.26; β = ?0.29; p = 0.002) and GR/GPx ratio (R ² = 0.25; β = ?0.28; p = 0.003). Black men with elevated blood pressure and albumin-to-creatinine ratio displayed a favorable NO synthesis capacity. This may be counteracted by increased inactivation of NO, although it was not linked to vascular or renal phenotypes. In white men, reduced NO synthesis capacity may lower NO bio-availability, thereby influencing the albumin-to-creatinine ratio.     

Curcumin-supplemented diets improve antioxidant enzymes and alter acetylcholinesterase genes expression level in <Emphasis Type="Italic">Drosophila melanogaster</Emphasis> model

Curcumin, a bioactive polyphenolic compound in turmeric (Curcuma longa) rhizomes has been shown to exert anti-aging properties with limited scientific basis. Hence, this study sought to examine the antioxidant and anti-cholinesterase activities of curcumin-supplemented diets as well as their molecular effect on superoxide dismutase (SOD) and acetylcholinesterase (AChE) genes expression level associated with lifespan extension in Drosophila melanogaster model. In this experiment, D. melanogaster (both genders) of 1 to 3 days old were fed diets either containing no curcumin (control) or supplemented with curcumin at 0.2 and 1.0 mg/g of diet for 7 days. Subsequently, the survival and locomotor activities were determined. In addition, we evaluated RT-PCR expressions of SOD and AChE mRNA genes. Furthermore, catalase, SOD and AChE activities were determined. Curcumin-supplemented diet improves survival ability but did not affect locomotor activity when compared with the control. In addition, there was a significant increase in SOD and catalase with a concomitant decrease of AChE activities when compared with the control. Furthermore, curcumin-supplemented diets suppress AChE mRNA expression but no alteration on SOD gene expression level was observed when compared with control. In conclusion, our present results suggest that a down-regulation of AChE gene expression with a concomitant decrease of AChE activity as well as improving antioxidant status could be some possible mechanism in which curcumin exert anti-aging potential and increases lifespan of D. melanogaster.     

Chemoprevention by Probiotics During 1,2-Dimethylhydrazine-Induced Colon Carcinogenesis in Rats

Background

Probiotics are believed to have properties that lower the risk of colon cancer. However, the mechanisms by which they exert their beneficial effects are relatively unknown.

Aim

To assess the impact of probiotics in preventing induction of colon carcinogenesis in rats.

Methods

The rats were divided into six groups viz., normal control, Lactobacillus plantarum (AdF10)-treated, Lactobacillus rhamnosus GG (LGG)-treated, 1,2-dimethylhydrazine (DMH)-treated, L. plantarum (AdF10) + DMH-treated and L. rhamnosus GG (LGG) + DMH-treated. Both the probiotics were supplemented daily at a dose of 2 × 10¹⁰ cells per day. DMH at a dose of 30 mg/kg body weight was administered subcutaneously twice a week for the first 4 weeks and then once every week for a duration of 16 weeks. Glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and catalase as protein expression of genes involved in apoptosis were assessed during DMH-induced colon carcinogenesis in rats.

Results

DMH treatment decreased the activity of GSH, GPx, GST, SOD and catalase. However, AdF10 and LGG supplementation to DMH-treated rats significantly increased the activity of these enzymes. Further, DMH treatment revealed alterations in the protein expressions of various genes involved in the p53-mediated apoptotic pathway such as p53, p21, Bcl-2, Bax, caspase-9 and caspase-3, which, however, were shifted towards normal control levels upon simultaneous supplementation with probiotics.

Conclusion

The present study suggests that probiotics can provide protection against oxidative stress and apoptotic-related protein disregulation during experimentally induced colon carcinogenesis.

     

Restorative effect of Eclipta alba in CCl4 induced hepatotoxicity in male albino rats

ObjectiveTo elucidate the restorative effect of the aqueous leaf extract (85%) of the traditional medicinal plant Eclipta alba (E. alba) against CCl₄ induced hepatotoxicity in male albino rats.MethodsRestorative activity was assessed using CCl₄-induced hepatic injury in rats by monitoring biochemical parameters. Biochemical markers of hepatic damage such as aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were assessed in serum. The oxidative stress was evaluated by measuring the levels of thiobarbutric acid reactive substance (TBARS), hydroperoxides, activity levels of enzymes viz. superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione-s-transferase (GST) in hepatic tissue.ResultsCCl₄ and olive oil mixture (1:1 dosage of 1 mL/kg b.w.) induced oxidative stress was indicated by elevated levels of TBARS and hydroperoxides, and augmented levels of serum AST, ALT and ALP. The depleted activity levels of antioxidant enzymes such as SOD, CAT, GPX and GST were found in CCl₄ induced animals. The aqueous leaf extract of E. alba (250 mg/kg b.w.) ameliorated the effects of CCl₄ and returned the alter levels of the biochemical markers near to the normal levels.ConclusionsThe study indicates that aqueous leaf extract of E. alba has potential restorative effect on CCl₄ induced hepatotoxicity in male albino rats.     

Antioxidant enzyme activities,lipid peroxidation,and total antioxidant status in children with Henoch–Schönlein purpura

The aim of this study was to assess the role of oxidative stress in the pathogenesis of Henoch–Schönlein purpura (HSP) vasculitis. The activities of catalase (CAT), arylesterase (ARYL), and paraoxonase (PON) as antioxidant enzymes and serum malondialdehyde (MDA) level as an indicator of lipid peroxidation, together with total antioxidant status (TAS), were measured in 29 children with HSP (mean age 9.3?±?2.7 years), both at the onset of the disease and at the remission period and in matched controls. Active-stage HSP had significantly higher MDA level (15.5?±?7.3 vs 7.8?±?3.9 nmol/l, respectively, P?P?P?=?0.042), ARYL (158?±?39 vs 212?±?52 U/l, P?P?=?0.002) activities compared with the control subjects. Although CAT (P?>?0.05) and PON (P?>?0.05) activities were found to be similar between active and remission stages of HSP, the active stage of the disease had significantly lower ARYL (P?=?0.011) and TAS (P?=?0.006) and higher MDA (P?r?=?0.433, P?=?0.019) and between CAT and C-reactive protein (r?=?0.386, P?=?0.035) in the active stage of HSP. No significant differences were detected in oxidant/antioxidant parameters between patients with or without renal, gastrointestinal, or joint involvement (P?>?0.05). Increased oxidative stress and lipid peroxidation may play important roles in the pathogenesis of HSP vasculitis. Antioxidant therapeutic interventions in long-lasting vasculitis and risk of atherosclerosis secondary to increased oxidant stress remain to be investigated.     

The effects of vitamin E on brain derived neurotrophic factor,tissues oxidative damage and learning and memory of juvenile hypothyroid rats

The effects of vitamin E (Vit E) on brain derived neurotrophic factor (BDNF) and brain tissues oxidative damage as well as on learning and memory impairments in juvenile hypothyroid rats were examined. The rats were grouped as: (1) Control; (2) Propylthiouracil (PTU); (3) PTU-Vit E and (4) Vit E. PTU was added to their drinking water (0.05%) during 6 weeks. Vit E (20 mg/kg) was daily injected (IP). Morris water maze (MWM) and passive avoidance (PA) were carried out. The animals were deeply anesthetized and the brain tissues were removed for biochemical measurements. PTU increased the escape latency and traveled path in MWM (P?<?0.001). It also shortened the latency to enter the dark compartment of PA as well as the time spent in the target quadrant in probe trial of MWM (P?<?0.01-P?<?0.001). All the effects of PTU were reversed by Vit E (P?<?0.01-P?<?0.001). PTU administration attenuated thiol and BDNF content as well as the activities of superoxide dismutase (SOD) and catalase (CAT) in the brain tissues while increased molondialdehyde (MDA). Moreover, Vit E improved BDNF, thiol, SOD and CAT while diminished MDA. The results of the present study showed that Vit E improved BDNF and prevented from brain tissues oxidative damage as well as learning and memory impairments in juvenile hypothyroid rats.     

Aberrant intestinal microbiota in individuals with prediabetes

Aims/hypothesis

Individuals with type 2 diabetes have aberrant intestinal microbiota. However, recent studies suggest that metformin alters the composition and functional potential of gut microbiota, thereby interfering with the diabetes-related microbial signatures. We tested whether specific gut microbiota profiles are associated with prediabetes (defined as fasting plasma glucose of 6.1–7.0 mmol/l or HbA_1c of 42–48 mmol/mol [6.0–6.5%]) and a range of clinical biomarkers of poor metabolic health.

Methods

In the present case–control study, we analysed the gut microbiota of 134 Danish adults with prediabetes, overweight, insulin resistance, dyslipidaemia and low-grade inflammation and 134 age- and sex-matched individuals with normal glucose regulation.

Results

We found that five bacterial genera and 36 operational taxonomic units (OTUs) were differentially abundant between individuals with prediabetes and those with normal glucose regulation. At the genus level, the abundance of Clostridium was decreased (mean log₂ fold change ?0.64 (SEM 0.23), p _adj ?=?0.0497), whereas the abundances of Dorea, [Ruminococcus], Sutterella and Streptococcus were increased (mean log₂ fold change 0.51 (SEM 0.12), p _adj ?=?5?×?10^?4; 0.51 (SEM 0.11), p _adj ?=?1?×?10^?4; 0.60 (SEM 0.21), p _adj ?=?0.0497; and 0.92 (SEM 0.21), p _adj ?=?4?×?10^?4, respectively). The two OTUs that differed the most were a member of the order Clostridiales (OTU 146564) and Akkermansia muciniphila, which both displayed lower abundance among individuals with prediabetes (mean log₂ fold change ?1.74 (SEM 0.41), p _adj ?=?2?×?10^?3 and ?1.65 (SEM 0.34), p _adj ?=?4?×?10^?4, respectively). Faecal transfer from donors with prediabetes or screen-detected, drug-naive type 2 diabetes to germfree Swiss Webster or conventional C57BL/6 J mice did not induce impaired glucose regulation in recipient mice.

Conclusions/interpretation

Collectively, our data show that individuals with prediabetes have aberrant intestinal microbiota characterised by a decreased abundance of the genus Clostridium and the mucin-degrading bacterium A. muciniphila. Our findings are comparable to observations in overt chronic diseases characterised by low-grade inflammation.

     

Physiological determinants of walking effort in older adults: should they be targets for physical activity intervention?

Older adults do not get enough physical activity increasing risk for chronic disease and loss of physical function. The purpose of this study was to determine whether neuromuscular, metabolic, and cardiorespiratory indicators of walking effort explain daily activity in community-dwelling older adults. Sixteen women and fourteen men, 78?±?8 years, performed a steady-state walk on a treadmill at 1.25 m s^?1 while muscle activation, heart rate, lactate, respiratory exchange ratio, oxygen consumption (VO₂), ventilation, and rating of perceived exertion (RPE) were recorded as markers of Walking Effort. Daily walking time, sitting/lying time, energy expenditure, and up-down transitions were recorded by accelerometers as markers of Daily Activity. Structural equation modeling was used to explore the relationship between the latent variables Walking Effort and Daily Activity controlling for age and BMI. Participants spent 9.4?±?1.9 h of the waking day sedentary and 1.9?±?0.6 h walking. In the structural equation model, the latent variable Walking Effort explained 64% of the variance in the Daily Activity latent variable (β?=?0.80, p?=?0.004). Walking Effort was identified by heart rate (β?=?0.64), ventilation (β?=?0.88), vastus lateralis activation (β?=?0.49), and lactate (β?=?0.58), all p?<?0.05, but not RPE or VO₂. Daily Activity was identified by stepping time (β?=?0.75) and up-down transitions (β?=?0.52), all p?<?0.05. Walking effort mediated the effects of age and BMI on older adults’ daily activity making physiological determinants of walking effort potential points of intervention.     

Alveolar Tidal recruitment/derecruitment and Overdistension During Four Levels of End-Expiratory Pressure with Protective Tidal Volume During Anesthesia in a Murine Lung-Healthy Model

Purpose

We compared respiratory mechanics between the positive end-expiratory pressure of minimal respiratory system elastance (PEEP_minErs) and three levels of PEEP during low-tidal-volume (6 mL/kg) ventilation in rats.

Methods

Twenty-four rats were anesthetized, paralyzed, and mechanically ventilated. Airway pressure (P_aw), flow (F), and volume (V) were fitted by a linear single compartment model (LSCM) P_aw(t)?=?E_rs?×?V(t)?+?R_rs?×?F(t)?+?PEEP or a volume- and flow-dependent SCM (VFDSCM) P_aw(t)?=?(E₁?+?E₂?×?V(t))?×?V(t) + (K₁?+?K₂?×?|F(t)|)?×?F(t)?+?PEEP, where E_rs and R_rs are respiratory system elastance and resistance, respectively; E₁ and E₂×?V are volume-independent and volume-dependent E_rs, respectively; and K₁ and K₂?×?F are flow-independent and flow-dependent R_rs, respectively. Animals were ventilated for 1 h at PEEP 0 cmH₂O (ZEEP); PEEP_minErs; 2 cmH₂O above PEEP_minErs (PEEP_minErs+2); or 4 cmH₂O above PEEP_minErs (PEEP_minErs+4). Alveolar tidal recruitment/derecruitment and overdistension were assessed by the index %E₂?=?100?×?[(E₂?×?V_T)/(E₁ + |E₂|?×?V_T)], and alveolar stability by the slope of E_rs(t).

Results

%E₂ varied between 0 and 30% at PEEP_minErs in most respiratory cycles. Alveolar Tidal recruitment/derecruitment (%E₂?<?0) and overdistension (%E₂?>?30) were predominant in the absence of PEEP and in PEEP levels higher than PEEP_minErs, respectively. The slope of E_rs(t) was different from zero in all groups besides PEEP_minErs+4.

Conclusions

PEEP_minErs presented the best compromise between alveolar tidal recruitment/derecruitment and overdistension, during 1 h of low-V_T mechanical ventilation.

     

Glucose effectiveness,but not insulin sensitivity,is improved after short-term interval training in individuals with type 2 diabetes mellitus: a controlled,randomised, crossover trial

Aims/hypothesis

The role of glucose effectiveness (S _G) in training-induced improvements in glucose metabolism in individuals with type 2 diabetes is unknown. The objectives and primary outcomes of this study were: (1) to assess the efficacy of interval walking training (IWT) and continuous walking training (CWT) on S _G and insulin sensitivity (S _I) in individuals with type 2 diabetes; and (2) to assess the association of changes in S _G and S _I with changes in glycaemic control.

Methods

Fourteen participants with type 2 diabetes underwent three trials (IWT, CWT and no training) in a crossover study. Exclusion criteria were exogenous insulin treatment, smoking, pregnancy, contraindications to structured physical activity and participation in recurrent training (>90 min/week). The trials were performed in a randomised order (computerised-generated randomisation). IWT and CWT consisted of ten supervised treadmill walking sessions, each lasting 60 min, over 2 weeks. IWT was performed as repeated cycles of 3 min slow walking and 3 min fast walking (aiming for 54% and 89% of \( \overset{\cdotp }{V}{\mathrm{O}}_{2\mathrm{peak}} \), respectively, which was measured during the last minute of each interval), and CWT was performed aiming for a moderate walking speed (73% of \( \overset{\cdot }{V}{\mathrm{O}}_{2\mathrm{peak}} \)). A two-step (pancreatic and hyperinsulinaemic) hyperglycaemic clamp was implemented before and after each trial. All data were collected in a hospitalised setting. Neither participants nor assessors were blinded to the trial interventions.

Results

Thirteen individuals completed all procedures and were included in the analyses. IWT improved S _G (mean ± SEM: 0.6 ± 0.1 mg kg^?1 min^?1, p < 0.05) but not S _I (p > 0.05), whereas CWT matched for energy expenditure and time duration improved neither S _G nor S _I (both p > 0.05). Changes in S _G, but not in S _I, were associated with changes in mean (β = ?0.62 ± 0.23, r ² = 0.17, p < 0.01) and maximum (β = ?1.18 ± 0.52, r ² = 0.12, p < 0.05) glucose levels during 24 h continuous glucose monitoring.

Conclusions/interpretation

Two weeks of IWT, but not CWT, improves S _G but not S _I in individuals with type 2 diabetes. Moreover, changes in S _G are associated with changes in glycaemic control. Therefore, increased S _G is likely an important mechanism by which training improves glycaemic control in individuals with type 2 diabetes.

Trial registration:

ClinicalTrials.gov NCT02320526

Funding:

CFAS is supported by a grant from TrygFonden. During the study period, the Centre of Inflammation and Metabolism (CIM) was supported by a grant from the Danish National Research Foundation (DNRF55). The study was further supported by grants from Diabetesforeningen, Augustinusfonden and Krista og Viggo Petersens Fond. CIM/CFAS is a member of DD2—the Danish Center for Strategic Research in Type 2 Diabetes (the Danish Council for Strategic Research, grant no. 09–067009 and 09–075724).

     

<Emphasis Type="Italic">Vegf-A</Emphasis> mRNA transfection as a novel approach to improve mouse and human islet graft revascularisation

Aims/hypothesis

The initial avascular period following islet transplantation seriously compromises graft function and survival. Enhancing graft revascularisation to improve engraftment has been attempted through virus-based delivery of angiogenic triggers, but risks associated with viral vectors have hampered clinical translation. In vitro transcribed mRNA transfection circumvents these risks and may be used for improving islet engraftment.

Methods

Mouse and human pancreatic islet cells were transfected with mRNA encoding the angiogenic growth factor vascular endothelial growth factor A (VEGF-A) before transplantation under the kidney capsule in mice.

Results

At day 7 post transplantation, revascularisation of grafts transfected with Vegf-A (also known as Vegfa) mRNA was significantly higher compared with non-transfected or Gfp mRNA-transfected controls in mouse islet grafts (2.11- and 1.87-fold, respectively) (vessel area/graft area, mean?±?SEM: 0.118?±?0.01 [n?=?3] in Vegf-A mRNA transfected group (VEGF) vs 0.056?±?0.01 [n?=?3] in no RNA [p?<?0.05] vs 0.063?±?0.02 [n?=?4] in Gfp mRNA transfected group (GFP) [p?<?0.05]); EndoC-bH3 grafts (2.85- and 2.48-fold. respectively) (0.085?±?0.02 [n?=?4] in VEGF vs 0.030?±?0.004 [n?=?4] in no RNA [p?<?0.05] vs 0.034?±?0.01 [n?=?5] in GFP [p?<?0.05]); and human islet grafts (3.17- and 3.80-fold, respectively) (0.048?±?0.013 [n?=?3] in VEGF vs 0.015?±?0.0051 [n?=?4] in no RNA [p?<?0.01] vs 0.013?±?0.0046 [n?=?4] in GFP [p?<?0.01]). At day 30 post transplantation, human islet grafts maintained a vascularisation benefit (1.70- and 1.82-fold, respectively) (0.049?±?0.0042 [n?=?8] in VEGF vs 0.029?±?0.0052 [n?=?5] in no RNA [p?<?0.05] vs 0.027?±?0.0056 [n?=?4] in GFP [p?<?0.05]) and a higher beta cell volume (1.64- and 2.26-fold, respectively) (0.0292?±?0.0032 μl [n?=?7] in VEGF vs 0.0178?±?0.0021 μl [n?=?5] in no RNA [p?<?0.01] vs 0.0129?±?0.0012 μl [n?=?4] in GFP [p?<?0.001]).

Conclusions/interpretation

Vegf-A mRNA transfection before transplantation provides a promising and safe strategy to improve engraftment of islets and other cell-based implants.

     

Mast Cells and Serotonin Synthesis Modulate Chagas Disease in the Colon: Clinical and Experimental Evidence

Background

Trypanosoma cruzi (T. cruzi) infects millions of Latin Americans each year and can induce chagasic megacolon. Little is known about how serotonin (5-HT) modulates this condition. Aim We investigated whether 5-HT synthesis alters T. cruzi infection in the colon.

Materials and Methods

Forty-eight paraffin-embedded samples from normal colon and chagasic megacolon were histopathologically analyzed (173/2009). Tryptophan hydroxylase 1 (Tph1) knockout (KO) mice and c-Kit^W-sh mice underwent T. cruzi infection together with their wild-type counterparts. Also, mice underwent different drug treatments (16.1.1064.60.3).

Results

In both humans and experimental mouse models, the serotonergic system was activated by T. cruzi infection (p?<?0.05). While treating Tph1KO mice with 5-HT did not significantly increase parasitemia in the colon (p?>?0.05), rescuing its synthesis promoted trypanosomiasis (p?<?0.01). T. cruzi-related 5-HT release (p?<?0.05) seemed not only to increase inflammatory signaling, but also to enlarge the pericryptal macrophage and mast cell populations (p?<?0.01). Knocking out mast cells reduced trypanosomiasis (p?<?0.01), although it did not further alter the neuroendocrine cell number and Tph1 expression (p?>?0.05). Further experimentation revealed that pharmacologically inhibiting mast cell activity reduced colonic infection (p?<?0.01). A similar finding was achieved when 5-HT synthesis was blocked in c-Kit^W-sh mice (p?>?0.05). However, inhibiting mast cell activity in Tph1KO mice increased colonic trypanosomiasis (p?<?0.01).

Conclusion

We show that mast cells may modulate the T. cruzi-related increase of 5-HT synthesis in the intestinal colon.

     

Systematic review assessing the effectiveness of dietary intervention on gut microbiota in adults with type 2 diabetes

Aims/hypothesis

Despite improved understanding of the pathophysiology of type 2 diabetes mellitus, explanations for individual variability in disease progression and response to treatment are incomplete. The gut microbiota has been linked to the pathophysiology of type 2 diabetes mellitus and may account for this variability. We conducted a systematic review to assess the effectiveness of dietary and physical activity/exercise interventions in modulating the gut microbiota and improving glucose control in adults with type 2 diabetes mellitus.

Methods

A systematic search was conducted to identify studies reporting on the effect of dietary and physical activity/exercise interventions on the gut microbiota and glucose control in individuals with a confirmed diagnosis of type 2 diabetes mellitus. Study characteristics, methodological quality and details relating to interventions were captured using a data-extraction form. Meta-analyses were conducted where sufficient data were available, and other results were reported narratively.

Results

Eight studies met the eligibility criteria of the systematic review. No studies were found that reported on the effects of physical activity/exercise on the gut microbiota and glucose control. However, studies reporting on dietary interventions showed that such interventions were associated with modifications to the composition and diversity of the gut microbiota. There was a statistically significant improvement in HbA_1c (standardised mean difference [SMD] ?2.31 mmol/mol [95% CI ?2.76, ?1.85] [0.21%; 95% CI ?0.26, ?0.16]; I²?=?0%, p?<?0.01), but not in fasting blood glucose (SMD ?0.25 mmol/l [95% CI ?0.85, 0.35], I²?=?87%, p?>?0.05), fasting insulin (SMD ?1.82 pmol/l [95% CI ?7.23, 3.60], I²?=?54%, p?>?0.05) or HOMA-IR (SMD ?0.15 [95% CI ?0.63, 0.32], I²?=?69%, p?>?0.05) when comparing dietary interventions with comparator groups. There were no significant changes in the relative abundance of bacteria in the genera Bifidobacterium (SMD 1.29% [95% CI ?4.45, 7.03], I²?=?33%, p?>?0.05), Roseburia (SMD ?0.85% [95% CI ?2.91, 1.21], I²?=?79%, p?>?0.05) or Lactobacillus (SMD 0.04% [95% CI ?0.01, 0.09], I²?=?0%, p?>?0.05) when comparing dietary interventions with comparator groups. There were, however, other significant changes in the gut microbiota, including changes at various taxonomic levels, including phylum, family, genus and species, Firmicutes:Bacteroidetes ratios and changes in diversity matrices (α and β). Dietary intervention had minimal or no effect on inflammation, short-chain fatty acids or anthropometrics.

Conclusions/interpretation

Dietary intervention was found to modulate the gut microbiota and improve glucose control in individuals with type 2 diabetes. Although the results of the included studies are encouraging, this review highlights the need for further well-conducted interventional studies to inform the clinical use of dietary interventions targeting the gut microbiota.

     

<Emphasis Type="Italic">Rhodiola rosea</Emphasis> extends lifespan and improves stress tolerance in silkworm, <Emphasis Type="Italic">Bombyx mori</Emphasis>

The root of Rhodiola rosea is widely used in Traditional Chinese Medicine. The extract from R. rosea is reported to extend the lifespan of yeast, nematode, and fruit fly. However, the molecular mechanism is not fully understood. Here, we tested whether R. rosea extends the lifespan of the silkworm. An aqueous extract of R. rosea significantly prolonged the lifespan of the silkworm, without affecting its daily food intake, body weight, or fecundity, suggesting that R. rosea did not exhibit obvious side effects. Rhodiola rosea extract also enhanced the stress resistance in the silkworm, against heat stress (37 °C) and starvation. The R. rosea extract increased the activity of the major antioxidant enzymes, glutathione S-transferase and catalase, and altered the content of glutathione and malondialdehyde. Rhodiola rosea increased the expression of BmFoxO, which is a downstream regulator of insulin/IGF-1 signaling (IIS) pathway in the silkworm. Our results showed that R. rosea extends lifespan, in which IIS pathway might be involved, and enhances stress resistance in the silkworm. Thus, the silkworm might be used as a novel animal model for lifespan study and efficacy evaluation of Traditional Chinese Medicines.     

An adult-based insulin resistance genetic risk score associates with insulin resistance,metabolic traits and altered fat distribution in Danish children and adolescents who are overweight or obese

Aims/hypothesis

A genetic risk score (GRS) consisting of 53 insulin resistance variants (GRS₅₃) was recently demonstrated to associate with insulin resistance in adults. We speculated that the GRS₅₃ might already associate with insulin resistance during childhood, and we therefore aimed to investigate this in populations of Danish children and adolescents. Furthermore, we aimed to address whether the GRS associates with components of the metabolic syndrome and altered body composition in children and adolescents.

Methods

We examined a total of 689 children and adolescents who were overweight or obese and 675 children and adolescents from a population-based study. Anthropometric data, dual-energy x-ray absorptiometry scans, BP, fasting plasma glucose, fasting serum insulin and fasting plasma lipid measurements were obtained, and HOMA-IR was calculated. The GRS₅₃ was examined for association with metabolic traits in children by linear regressions using an additive genetic model.

Results

In overweight/obese children and adolescents, the GRS₅₃ associated with higher HOMA-IR (β?=?0.109?±?0.050 (SE); p?=?2.73?×?10^?2), fasting plasma glucose (β?=?0.010?±?0.005 mmol/l; p?=?2.51?×?10^?2) and systolic BP SD score (β?=?0.026?±?0.012; p?=?3.32?×?10^?2) as well as lower HDL-cholesterol (β?=??0.008?±?0.003 mmol/l; p?=?1.23?×?10^?3), total fat-mass percentage (β?=??0.143?±?0.054%; p?=?9.15?×?10^?3) and fat-mass percentage in the legs (β?=??0.197?±?0.055%; p?=?4.09?×?10^?4). In the population-based sample of children, the GRS₅₃ only associated with lower HDL-cholesterol concentrations (β?=??0.007?±?0.003 mmol/l; p?=?1.79?×?10^?2).

Conclusions/interpretation

An adult-based GRS comprising 53 insulin resistance susceptibility SNPs associates with insulin resistance, markers of the metabolic syndrome and altered fat distribution in a sample of Danish children and adolescents who were overweight or obese.

     

Influence of hippocampal GABA<Subscript>B</Subscript> receptor inhibition on memory in rats with acute β-amyloid toxicity

The neurotransmitter γ-aminobutyric acid (GABA) is involved in the process of memory. It has been reported that the inhibition of GABA_B receptors has beneficial effects on cognition. The aim of this study was to investigate the role of CGP35348 (a GABA_B receptor antagonist) on dentate gyrus GABA_B receptor inhibition and its effects on learning and memory impairments that had been induced in adult male rats by microinjection of β-amyloid (Aβ). Seventy Wistar male rats were randomly divided into seven groups: control, sham (receiving the Aβ vehicle only), Aβ, Aβ + CGP35348 (1, 10, and 100 μg/μL), and CGP35348 alone (10 μg/μL). Memory impairment was induced by unilateral interventricular microinjection of Aβ (6 μg/6 μL). Rats were cannulated bilaterally in the dentate gyrus, and then, they were treated for 20 consecutive days. Learning and memory were assessed using the novel object recognition and passive avoidance learning tests. The discrimination index and the step-through latency were significantly increased in the Aβ + CGP35348 group in comparison to the Aβ only group (P?<?0.05 and P?<?0.01, respectively). Data showed that the discrimination index was decreased in the Aβ + CGP35348 group in comparison with the control group (P?<?0.05) and sham group (P?<?0.01). Moreover, the step-through latency was significantly decreased in the Aβ + CGP35348 group in comparison to the control and sham groups (P?<?0.01). Data from this study indicated that intra-hippocampal microinjection of the GABA_B receptor antagonist counteracts the learning, memory, and cognitive impairments induced by Aβ. It can be concluded that the GABA_B receptor antagonist is a possible therapeutic agent against the progression of acute Aβ toxicity-induced memory impairment.     

Association between arterial stiffness,disease activity and functional impairment in ankylosing spondylitis patients: a cross-sectional study

Cardiovascular risk is an important factor for increased morbidity and mortality in patients with ankylosing spondylitis. The aim of this study is to assess arterial stiffness in relation to the disease activity and functional limitation in patients with ankylosing spondylitis. Twenty-four patients (mean age 45.8?±?11.7 years) suffering of ankylosing spondylitis (disease duration 11.1?±?5.1 years) and 24 gender and age-matched healthy controls were included in the study. Clinical, biological, and functional status of ankylosing spondylitis patients was recorded. Arterial stiffness was assessed by measuring pulse wave velocity (PWV) and pulse wave analysis (PWA) was performed using applanation tonometry. We found significant differences between ankylosing spondylitis patients and healthy controls in regard to PWV (p?=?0.047), aortic augmentation pressure—AP (p?=?0.028), augmentation index—AIx (p?=?0.038) and aortic augmentation index adjusted for heart rate—AIx75 (p?=?0.011). PWV and AIx75 were significantly associated with the disease functioning score—BASFI (p?=?0.012, r?=?0.504; p?=?0.041, r?=?0.421). Aortic AP and augmentation indexes (AIx and AIx75) were all associated to ASDAS score (p?=?0.028, r?=?0.448; p?=?0.005, r?=?0.549; p?=?0.025, r?=?0.455). Our study showed that ankylosing spondylitis patients have a higher arterial stiffness than the age-matched controls, leading to an increased cardiovascular risk. We found that arterial stiffness is positively associated with disease activity and functional impairment. Chronic spondiloarthropaties should be screened for arterial stiffness, even in the absence of traditional cardiovascular risk factors, in order to benefit from primary prevention measures.     

Evaluation of work disability in Japanese patients with rheumatoid arthritis: from the TOMORROW study

To evaluate work disability and associated factors in patients with rheumatoid arthritis (RA) who participated in the TOMORROW study, a 10-year cohort study in Japan. Subjects in this cross-sectional analysis comprised 191 RA patients and 191 age- and sex-matched non-RA individuals. Work-related outcomes were measured using the Work Productivity and Activity Impairment questionnaire by employment status (full-time worker (FTW), employed ≥ 35 h/week; part-time worker (PTW), < 35 h/week; home worker (HW), non-employed). In addition, we assessed the EuroQol-5 Dimensions (EQ-5D) and Health Assessment Questionnaire (HAQ) to evaluate quality of life and activities of daily living. No significant differences were evident between groups in percentages of participants in each employment status (p =?0.11), percentages of absenteeism (FTW, p?=?1.00; PTW, p?=?0.29), presenteeism (FTW, p?=?0.23; PTW, p?=?0.54), overall work impairment (FTW, p?=?0.23; PTW, p?=?0.73), or percentage of activity impairment (AI) (FTW, p?=?0.62; PTW, p?=?0.60). In the HW group, percentage of AI was higher in RA patients than that in non-RA patients (p?<?0.01). Among RA patients, HW showed lower EQ-5D and higher HAQ than FTW or PTW (p?<?0.001 each). Higher disease activity was observed in HW than FTW (p <?0.01). In terms of the effect of biological disease-modifying anti-rheumatic drugs, no significant differences in work-related outcomes, health status, or daily activity were evident between users and non-users. No significant differences in employment status or work impairment were seen between RA and non-RA groups among paid workers. HW with RA showed more impaired daily activity and higher disease activity compared to working RA patients. Trial registration: University Hospital Medical Information Network Clinical Trials Registry: UMIN000003876. Registered 1 Jun 2010.     

Comparison of pulse wave velocity assessed by three different techniques: Arteriograph,Complior, and Echo-tracking

Arterial stiffness estimated by pulse wave velocity (PWV) is an independent predictor of cardiovascular morbidity and mortality. Although recommended by the current guidelines, clinical applicability of this parameter is difficult, due to differences between the various techniques used to measure it and to biological variability. Our aim was to compare PWV assessed by 3 different commercially available systems. 100 subjects (51 ± 16 years, 45 men) were evaluated using the 3 methods: an oscillometric technique (Arteriograph, PWV-A); a piezo-electric method (Complior, PWV-C); and an high-resolution ultrasound technique implemented with an Echo-tracking system (Aloka, PWV-E). Conventional biological markers were measured. Correlations of PWV measured by the 3 methods were poor (r = 0.39, r = 0.39, and r = 0.31 for PWV-A vs. PWV-C, PWV-A vs. PWV-E, and PWV-C vs. PWV-E, respectively, all p < 0.05). By Bland–Altman analysis, mean difference (±SD) of PWV-A vs. PWV-C was ?1.9 ± 2.0 m/s, of PWV-A vs. PWV-E ?3.6 ± 1.9 m/s, and of PWV-C vs. PWV-E ?2.7 ± 1.9 m/s, with a wide coefficient of variation (22.3, 25.7, and 25.7 %, respectively). As expected, PWV-A, PWV-C, and PWV-E correlated with other arterial stiffness parameters, such as intima-media thickness (r = 0.22, r = 0.22, and r = 0.36, respectively), E _p (r = 0.37, r = 0.26, and r = 0.94, respectively), and augmentation index measured by Arteriograph method (r = 0.66, r = 0.35, and r = 0.26, respectively); all p < 0.05. Assessment of PWV is markedly dependent on the technique used to measure it, related to various methods for measuring traveled distance of the arterial wave. Our results suggest the urgent need to establish reference values of PWV for each of these techniques, separately, to be used in routine clinical practice.