Evaluation of hepatoprotective effect of methanolic extract of Clitoria ternatea (Linn.) flower against acetaminophen-induced liver damage

Objective

To evaluate the hepatoprotective and antioxidant activity of Clitoria ternatea (C. ternatea) flower extract against acetaminophen-induced liver toxicity.

Methods

The antioxidant property of C. ternatea flower extract was investigated by employing established in vitro antioxidant assay. The C. ternatea flower extract was studied in this work for its hepatoprotective effect against acetaminophen-induced liver toxicity in mice. Activity was measured by monitoring the levels of aspartate aminotransferase, alanine aminotransferase, billirubin and glutathione with histopathological analysis.

Results

The amount of total phenolics and flavonoids were estimated to be 105.40±2.47 mg/g gallic acid equivalent and 72.21±0.05 mg/g catechin equivalent respectively. The antioxidant activity of C. ternatea flower extract was 68.9% at a concentration of 1 mg/mL and was also concentration dependant, with an IC₅₀ value of 327.00 µg/mL. The results of acetaminophen-induced liver toxicity experiment showed that mice treated with the extract (200 mg/kg) showed a significant decrease in alanine aminotransferase, aspartate aminotransferase, and bilirubin levels, which were all elevated in the paracetamol group (P<0.05). Meanwhile, the level of glutathione was found to be restored in extract treated animals compared to the groups treated with acetaminophen alone (P<0.05). Therapy of extract also showed its protective effect on histopathological alterations and supported the biochemical finding.

Conclusion

The present work confirmed the hepatoprotective effect of C. ternatea flower against model hepatotoxicant acetaminophen.     

Benefit of a low-fat over high-fat diet on vascular health during alternate day fasting

Background:

Alternate day fasting (ADF) with a low-fat (LF) diet improves brachial artery flow-mediated dilation (FMD). Whether these beneficial effects can be reproduced with a high-fat (HF) diet remains unclear.

Objective:

This study compared the effects of ADF-HF to ADF-LF regimens on FMD. The role that adipokines have in mediating this effect was also investigated.

Methods:

Thirty-two obese subjects were randomized to an ADF-HF (45% fat) or ADF-LF diet (25% fat), consisting of two phases: (1) a 2-week baseline weight maintenance period and (2) an 8-week ADF weight loss period. Food was provided throughout the study.

Results:

Body weight was reduced (P<0.0001) in the ADF-HF (4.4±1.0 kg) and ADF-LF group (3.7±0.7 kg). FMD decreased (P<0.05) by ADF-HF relative to baseline (7±1 to 5±2%) and increased (P<0.05) by ADF-LF (5±1 to 7±2%). Blood pressure remained unchanged in both groups. Adiponectin increased (P<0.05) in the ADF-HF (43±7%) and ADF-LF group (51±7%). Leptin and resistin decreased (P<0.05) in the ADF-HF (32±5% 23±5%) and ADF-LF group (30±3% 27±4%). Increases in adiponectin were associated with augmented FMD in the ADF-LF group only (r=0.34, P=0.03).

Conclusion:

Thus, improvements in FMD with ADF may only occur with LF diets and not with HF diets, and adipokines may not have a significant role in mediating this effect.     

A comparison of effects of lard and hydrogenated vegetable shortening on the development of high-fat diet-induced obesity in rats

Background:

Obesity is associated with increased consumption and preference for dietary fat. Experimental models of fat-induced obesity use either lard or vegetable shortening. Yet, there are no direct comparisons of these commonly used fat sources, or the influence of their fatty acid composition, on the development of diet-induced obesity.

Objective:

To compare the effects of lard and hydrogenated vegetable-shortening diets, which differ in their fatty acid composition, on weight gain and the development of obesity and insulin resistance in rats.

Methods and design:

Male Wistar rats were fed ad libitum for 14 weeks high-fat diets containing either (1) high vegetable fat (HVF, 60 kcal% from vegetable shortening) or (2) high lard fat (HLF, 60 kcal% from lard). Rats fed normal-fat (NF, 16 kcal% from vegetable shortening) diet served as control. Body weight, food intake, adipose tissue mass, serum 25[OH]D₃, glucose, insulin and fatty acid composition of diets were measured.

Results:

Rats fed either of the two high-fat diets had higher energy intake, weight gain and fat accretion than rats fed normal-fat diet. However, rats fed the HLF diet consumed more calories and gained more weight and body fat with greater increases of 32% in total (158.5±8.2 vs 120.2±6.6 g, P<0.05), 30% in visceral (104.4±5.2 vs 80.3±4.2 g, P<0.05) and 36% in subcutaneous fat mass (54.1±3.6 vs 39.9±3.1 g, P<0.05), compared with rats fed the HVF diet. Higher visceral adiposity was positively correlated with serum insulin (r=0.376, P<0.05) and homeostatic model assessment insulin resistance (r=0.391, P<0.05).

Conclusion:

We conclude that lard-based high-fat diets accentuate the increase in weight gain and the development of obesity and insulin resistance more than hydrogenated vegetable-shortening diets. These results further point to the importance of standardizing fatty acid composition and type of fat used in determining outcomes of consuming high-fat diets.     

Randomized trial of nutrition education added to internet-based information and exercise at the work place for weight loss in a racially diverse population of overweight women

Objective:

Obesity in the United States is highly prevalent, approaching 60% for black women. We investigated whether nutrition education sessions at the work place added to internet-based wellness information and exercise resources would facilitate weight and fat mass loss in a racially diverse population of overweight female employees.

Methods:

A total of 199 (average body mass index 33.9±6.3 kg m⁻²) nondiabetic women (57% black) at our institution were randomized to a 6-month program of either internet-based wellness information (WI) combined with dietitian-led nutrition education group sessions (GS) weekly for 3 months and then monthly with shift in emphasis to weight loss maintenance (n=99) or to WI alone (n=100). All were given access to exercise rooms convenient to their work site. Fat mass was measured by dual-energy X-ray absorptiometry.

Results:

WI+GS subjects lost more weight than WI subjects at 3 months (−2.2±2.8 vs −1.0±3.0 kg, P>0.001). Weight (−2.7±3.9 vs −2.0±3.9 kg) and fat mass (−2.2±3.1 vs −1.7±3.7 kg) loss at 6 months was significant for WI+GS and WI groups (both P<0.001), but without significant difference between groups (both P>0.10); 27% of the WI+GS group achieved ⩾5% loss of initial weight as did 18% of the WI group (P=0.180). Blacks and whites similarly completed the study (67 vs 74%, P=0.303), lost weight (−1.8±3.4 vs −3.3±5.2 kg, P=0.255) and fat mass (−1.6±2.7 vs −2.5±4.3 kg, P=0.532), and achieved ⩾5% loss of initial weight (21 vs 32%, P=0.189), irrespective of group assignment.

Conclusion:

Overweight women provided with internet-based wellness information and exercise resources at the work site lost weight and fat mass, with similar achievement by black and white women. Additional weight loss benefit of nutrition education sessions, apparent at 3 months, was lost by 6 months and may require special emphasis on subjects who fail to achieve weight loss goals to show continued value.     

Lycopene supplementation reduces TNF-α via RAGE in the kidney of obese rats

Background:

The kidney is a target organ for injuries caused by advanced glycation end products (AGEs) in obesity. The receptor of AGEs (RAGE) is proinflammatory and appears to have a role in the pathogenesis of renal disease due to obesity.

Objective:

The aim was to verify the effect of obesity on renal damage and the effect of lycopene on these complications

Design and Methods:

Male Wistar rats were randomly assigned to receive a control diet (C, n=7) or a high-fat diet plus sucrose (HD+S, n=14) for 6 weeks. After this period, the HD+S animals were randomized into two groups: HD+S (n=7) and HD+S supplemented with lycopene (HD+S+L, n=7). The animals received maize oil (C and HD+S) or lycopene (HD+S+L) for a 6-week period.

Results:

The HD+S and HD+S+L animals demonstrated insulin resistance (OGTT glucose after 150 min; C: 117.6±3.9<HD+S: 138.1±5.1=HD+S+L: 137.8±5.2 mg dl⁻¹; P=0.01); however, no changes were seen in fasting glucose, plasma lipids, blood pressure or renal function. Renal concentrations of RAGE and TNF-α increased in the HD+S group and lycopene supplementation restored these to control group values (RAGE: C: 3.1±0.3=DH+S+L: 3.1±0.3<DH+S: 3.6±0.4 μg g⁻¹; P=0.014; TNF-α: C: 227.8±2.7=DH+S+L: 227.4±2.2<DH+S: 238.7±3.0 pg/ml; P=0.014).

Conclusions:

Lycopene may be beneficial in the prevention and treatment of oxidative stress and inflammation in the kidney due to obesity.     

Microwave ablation using 915-MHz and 2.45-GHz systems: what are the differences?

Objectives

This study was conducted to evaluate differences between 915-MHz and 2.45-GHz microwave ablation (MWA) systems in the ablation of hepatic tumours.

Methods

A retrospective analysis of patients undergoing hepatic tumour MWA utilizing two different systems over a 10-month period was carried out.

Results

Data for a total of 48 patients with a mean age of 58 ± 1.24 years were analysed. A total of 124 tumours were ablated; 72 tumours were ablated with a 915-MHz system and 52 with a 2.45-GHz system. Mean tumour diameters were 1.7 ± 0.1 cm in the 915-MHz group and 2.5 ± 0.2 cm in the 2.45-GHz group (P < 0.01). Mean ablation time per burn was 8.1 ± 0.3 min in the 915-MHz group and 4.0 ± 0.1 min in the 2.45-GHz group (P < 0.01). The mean number of burns per lesion was 2.0 ± 0.1 in the 915-MHz group and 1.7 ± 0.1 in the 2.45-GHz group (P < 0.05). The mean ablation time per lesion was 9.7 ± 0.7 min in the 915-MHz group, and 6.6 ± 0.6 min in the 2.45-GHz group (P < 0.01). The 2.45-GHz system demonstrated a better correlation between ablation time and tumour size (r² = 0.6222) than the 915-MHz system; (r² = 0.0696). Mean total energy applied per lesion, and energy applied per cm, were greater with the 915-MHz system (P < 0.05 and P < 0.01, respectively). Total energy applied per lesion was similarly correlated for the 2.45-GHz (r² = 0.6263) and 915-MHz (r² = 0.7012) systems. Mean total energy applied per cm/min was greater with the 2.45-GHz system (P < 0.05).

Conclusions

Both 915-MHz and 2.45-GHz MWA systems achieve reproducible hepatic tumour ablation. The 2.45-GHz system achieves equivalent, but more predictable and faster ablations using a single antenna system.     

The Microvasculature in Chronic Kidney Disease

Summary

Background and objectives

Individuals with chronic kidney disease (CKD) stages 3 to 5 have an increased risk of cardiac and other vascular disease. Here we examined the association of CKD 3 to 5 with small vessel caliber.

Design, setting, participants, & measurements

This was a cross-sectional observational study of 126 patients with CKD stages 3 to 5 (estimated GFR [eGFR] <60 ml/min per 1.73 m²) and 126 age- and gender-matched hospital patients with CKD 1 or 2. Retinal vessel diameters were measured from digital fundus images by a trained grader using a computer-assisted method and summarized as the central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE).

Results

Patients with CKD 3 to 5 had a smaller mean CRAE and CRVE than hospital controls (139.4 ± 17.8 μm versus 148.5 ± 16.0 μm, P < 0.001; and 205.0 ± 30.7 μm versus 217.4 ± 25.8 μm, respectively; P = 0.001). CRAE and CRVE decreased progressively with each stage of renal failure CKD1–2 to 5 (P for trend = 0.08 and 0.04, respectively). CKD and hypertension were independent determinants of arteriolar narrowing after adjusting for age, gender, diabetes, dyslipidemia, and smoking history. Patients with CKD 5 and diabetes had a larger mean CRAE and CRVE than nondiabetics (141.4 ± 14.9 μm versus 132.9 ± 14.2 μm; 211.1 ± 34.4 μm versus 194.8 ± 23.8 μm).

Conclusions

The microvasculature is narrowed in patients with reduced eGFR.     

Is the liver kinetic growth rate in ALPPS unprecedented when compared with PVE and living donor liver transplant? A multicentre analysis

Background

The clinical perspective on hepatic growth is limited. The goal of the present study was to compare hepatic hypertrophy and the kinetic growth rate(KGR) in patients after the ALPPS (Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy) procedure, portal vein embolization (PVE) and living donor liver transplantation.

Methods

Volumetry and KGR of the future liver remnant (FLR) were compared from (15) patients undergoing ALPPS, (53) patients undergoing PVE, (90) recipients of living donor liver grafts and (93) donors of living donor liver grafts.

Results

The degree of hypertrophy was significantly greater after ALPPS (84.3 ± 7.8%) than after PVE (36.0 ± 27.2%) (P < 0.001). The KGR was also significantly greater for ALPPS [32.7 ± 13.6 cubic centimetres (cc)/day] (10.8 ± 4.5%/day) compared with PVE (4.4 ± 3.2 cc/day) (0.98 ± 0.75%/day) (P < 0.001). The FLR of living donor donors had the greatest degree of hypertrophy (107.5 ± 39.2%) and was greater than after ALPPS (P = 0.02), PVE (P < 0.001) and in living donor-recipient grafts (P < 0.001). KGR (cc/day) was greater in FLR of living donor donors compared with both ALPPS (P < 0.001) and PVE (P < 0.001). The KGR in patients undergoing ALPPS and living donor liver transplantation had a linear relationship with the size of FLR.

Conclusion

FLR hypertrophy and KGR were greater after ALPPS than PVE. However, the degree of hypertrophy after ALPPS is not unprecedented, as KGR in the FLR from living donor donors is equal to or greater than after ALPPS. The KGR of the FLR in patients after ALPPS and living donor donors correlates directly with the size of the FLR.     

Substitutions in Penicillin-Binding Protein 1 in Amoxicillin-Resistant Helicobacter pylori Strains Isolated from Korean Patients

Background/Aims

A worldwide increase in amoxicillin resistance in Helicobacter pylori is having an adverse effect on eradication therapy. In this study, we investigated the mechanism of the amoxicillin resistance of H. pylori in terms of amino acid substitutions in penicillin-binding protein 1 (PBP1).

Methods

In total, 150 H. pylori strains were isolated from 144 patients with chronic gastritis, peptic ulcers, or stomach cancer. The minimum inhibitory concentrations (MICs) of the strains were determined with a serial 2-fold agar dilution method. The resistance breakpoint for amoxicillin was defined as >0.5 µg/mL.

Results

Nine of 150 H. pylori strains showed amoxicillin resistance (6%). The MIC values of the resistant strains ranged from 1 to 4 µg/mL. A PBP1 sequence analysis of the resistant strains revealed multiple amino acid substitutions: Val16→Ile, Val45→Ile, Ser414→Arg, Asn562→Tyr, Thr593→Ala, Gly595→Ser, and Ala599→Thr. The natural transformation of these mutated genes into amoxicillin-sensitive strains was performed in two separate pbp1 gene segments. A moderate increase in the amoxicillin MIC was observed in the segment that contained the penicillin-binding motif of the C-terminal portion, the transpeptidase domain.

Conclusions

pbp1 mutation affects the amoxicillin resistance of H. pylori through the transfer of the penicillin-binding motif.     

Association of aortic stiffness to brain natriuretic peptide in children before and after device closure of patent ductus arteriosus

Objectives

We evaluated the influence of device closure for patent ductus arteriosus (PDA) on the aortic stiffness index (ASI) and brain natriuretic peptide (BNP) and their association with cardiac function.

Patients and methods

ASI and echocardiography assessment before and after treatment (16 ± 9 months) in 48 children with PDA (mean age 10 ± 4.5) and 52 control children (mean age 9.7 ± 4.6). BNP level was measured pre-closure for all children, and was measured six months after closure only for children with PDA.

Results

ASI was higher in PDA patients than in controls (P < 0.001). ASI correlated with age (P < 0.05), LVEF% (P < 0.01), E/E′ (<0.03), pulmonary artery pressure (P < 0.001), and BNP (P < 0.001). ASI and BNP significantly decreased after closure (P < 0.001). ASI and BNP were independent predictors for post-closure systolic dysfunction (P < 0.001and <0.005, respectively). Receiver operating curve (ROC) analysis showed that ASI ⩾ 13.5, BNP level ⩾75 pg/ml and basal mean pulmonary artery pressure (PAP) ⩾ 23 were powerful predictors for post-closure systolic function.

Conclusion

ASI is significantly associated with BNP and basal PAP in children with PDA. After device closure, aortic distensibility improved significantly and was associated with significant improvement in both systolic and diastolic functions. ASI can be used for monitoring the course of patients with PDA, and may give opportunities for early intervention.     

The LiMAx test: a new liver function test for predicting postoperative outcome in liver surgery

Background:

Liver failure has remained a major cause of mortality after hepatectomy, but it is difficult to predict preoperatively. This study describes the introduction into clinical practice of the new LiMAx test and provides an algorithm for its use in the clinical management of hepatic tumours.

Methods:

Patients with hepatic tumours and indications for hepatectomy were investigated perioperatively with the LiMAx test. In one patient, analysis of liver volume was carried out with preoperative three-dimensional virtual resection.

Results:

A total of 329 patients with hepatic tumours were evaluated for hepatectomy. Blinded preoperative LiMAx values were significantly higher before resection (n= 139; mean 351 µg/kg/h, range 285–451 µg/kg/h) than before refusal (n= 29; mean 299 µg/kg/h, range 223–376 µg/kg/h; P= 0.009). In-hospital mortality rates were 38.1% (8/21 patients), 10.5% (2/19 patients) and 1.0% (1/99 patients) for postoperative LiMAx of <80 µg/kg/h, 80–100 µg/kg/h and >100 µg/kg/h, respectively (P < 0.0001). A decision tree was developed to avoid critical values and its prospective preoperative application revealed a reduction in mortality from 9.4% to 3.4% (P= 0.019).

Discussion:

The LiMAx test can validly determine liver function capacity and is feasible in every clinical situation. Combination with virtual resection could enable the calculation of residual liver function. The LiMAx decision tree algorithm for hepatectomy might significantly improve preoperative evaluation and postoperative outcome in liver surgery.     

Bucillamine improves hepatic microcirculation and reduces hepatocellular injury after liver warm ischaemia-reperfusion injury

Background:

Liver transplantation and resection surgery involve a period of ischaemia and reperfusion to the liver which initiates an inflammatory cascade resulting in liver and remote organ injury. Bucillamine is a low-molecular-weight thiol antioxidant that is capable of rapidly entering cells.

Methods:

The effect of bucillamine was studied in a rat model of liver ischaemia–reperfusion injury with 45 min of partial (70%) liver ischaemia and at 3 and 24 h of reperfusion. Controls included ischaemia-reperfusion (I/R) only, sham and bucillamine alone (without ischaemia reperfusion). Liver injury was assessed by serum transaminases (AST and ALT). Sinusoidal blood flow and hepatocyte apoptosis were measured using intravital microscopy (IVM).

Results:

The hepatocellular injury of I/R produced a markedly elevated serum AST which was reduced with bucillamine (2072.5 ± 511.79 vs. 932 ± 200.8, P < 0.05) at 3 h reperfusion. Bucillamine treatment with I/R also increased parenchymal blood flow [red blood cell (RBC) velocity 242.66 ± 16.86 vs. 181.11 ± 17.59, at the end of 3 h of reperfusion) and reduced hepatocyte necrosis/apoptosis at 3 h as well as 24 h (P > 0.001).

Conclusion:

Bucillamine reduces the hepatocellular injury of liver ischaemia reperfusion and improves parenchymal perfusion.     

β-T594M epithelial sodium channel gene polymorphism and essential hypertension in individuals of Indo-Aryan ancestry in Northern India

Background

The T594M variant of the β-subunit of the sodium epithelial channel (ENaC) gene may contribute to hypertension in individuals of Indo-Aryan origin.

Methods

Present study was performed to assess the role of the ENaC gene variant as an independent risk factor for hypertension in subjects of Indo-Aryan ancestry. A total of 150 patients of recently detected essential hypertension and 150 matched controls were genotyped for the T594M polymorphism of the ENaC gene by PCR–RFLP method.

Results

β-T594M mutation was found to be non-polymorphic. There was major genotype call in both the groups i.e. cases and controls. Other phenotypic parameters like age, sex and body mass index were also similar among hypertensive patients and controls (P > 0.05). Hypertensive patients had significantly higher total cholesterol and triglycerides compared with controls (P < 0.0001).

Conclusion

These results do not suggest an important role for the T594M variant of the ENaC gene contributing to either the development or severity of hypertension in subjects of Indo-Aryan ancestry.     

Left Ventricular Synchrony and Function in Pediatric Patients with Definitive Pacemakers

Background

Chronic right ventricular pacing (RVP) induces a dyssynchronous contraction pattern, producing interventricular and intraventricular asynchrony. Many studies have shown the relationship of RVP with impaired left ventricular (LV) form and function.

Objective

The aim of this study was to evaluate LV synchrony and function in pediatric patients receiving RVP in comparison with those receiving LV pacing (LVP).

Methods

LV systolic and diastolic function and synchrony were evaluated in 80 pediatric patients with either nonsurgical or postsurgical complete atrioventricular block, with pacing from either the RV endocardium (n = 40) or the LV epicardium (n = 40). Echocardiographic data obtained before pacemaker implantation, immediately after it, and at the end of a mean follow-up of 6.8 years were analyzed.

Results

LV diastolic function did not change in any patient during follow-up. LV systolic function was preserved in patients with LVP. However, in children with RVP the shortening fraction and ejection fraction decreased from medians of 41% ± 2.6% and 70% ± 6.9% before implantation to 32% ± 4.2% and 64% ± 2.5% (p < 0.0001 and p < 0.0001), respectively, at final follow-up. Interventricular mechanical delay was significantly larger with RVP (66 ± 13 ms) than with LVP (20 ± 8 ms). Similarly, the following parameters were significantly different in the two groups: LV mechanical delay (RVP: 69 ± 6 ms, LVP: 30 ± 11 ms, p < 0.0001); septal to lateral wall motion delay (RVP: 75 ± 19 ms, LVP: 42 ± 10 ms, p < 0.0001); and, septal to posterior wall motion delay (RVP: 127 ± 33 ms, LVP: 58 ± 17 ms, p < 0.0001).

Conclusion

Compared with RV endocardium, LV epicardium is an optimal site for pacing to preserve cardiac synchrony and function.     

Measurement of Intrahepatic Pressure during Microwave Ablation in an Ex Vivo Bovine Liver Model

Background/Aims

We experimented with different ablation methods and two types of microwave antennas to determine whether microwave ablation (MWA) increases intrahepatic pressure and to identify an MWA protocol that avoids increasing intrahepatic pressure.

Methods

MWA was performed using either a single-step standard ablation or a stepwise increment ablation paired with either a 16-gauge (G) 2-cm antenna or a 14G 4-cm antenna. We compared the maximum pressures and total ablation volumes.

Results

The mean maximum intrahepatic pressures and ablation volumes were as follows: 16G single-step: 37±33.4 mm Hg and 4.63 cm³; 16G multistep: 31±18.7 mm Hg and 3.75 cm³; 14G single-step: 114±45.4 mm Hg and 15.33 cm³; and 14G multistep: 106±43.8 mm Hg and 10.98 cm³. The intrahepatic pressure rose during MWA, but there were no statistically significant differences between the single and multistep methods when the same gauge antennae were used. The total ablation volume was different only in the 14G groups (p<0.05).

Conclusions

We demonstrated an increase in intrahepatic pressure during MWA. The multistep method may be used to prevent increased intrahepatic pressure after applying the proper power.     

Effects of a Renal Rehabilitation Exercise Program in Patients with CKD: A Randomized,Controlled Trial

Background and objectives

Patients with CKD have a high prevalence of cardiovascular disease associated with or exacerbated by inactivity. This randomized, controlled study investigated whether a renal rehabilitation exercise program for patients with stages 3 or 4 CKD would improve their physical function and quality of life.

Design, setting, participants, & measurements

In total, 119 adults with CKD stages 3 and 4 were randomized, and 107 of these patients proceeded to usual care or the renal rehabilitation exercise intervention consisting of usual care plus guided exercise two times per week for 12 weeks (24 sessions). Physical function was determined by three well established performance-based tests: 6-minute walk test, sit-to-stand test, and gait-speed test. Health-related quality of life was assessed by the RAND 36-Item Short Form Health Survey.

Results

At baseline, no differences in self-reported level of activity, 6-minute walk test, and sit-to-stand test scores were observed between the usual care (n=48) and renal rehabilitation exercise (n=59) groups, although baseline gait-speed test score was higher in the renal rehabilitation exercise group (P<0.001). At follow-up, the renal rehabilitation exercise group but not the usual care group showed significant improvements in the 6-minute walk test (+210.4±266.0 ft [19% improvement] versus −10±219.9 ft; P<0.001), the sit-to-stand test (+26.9±27% of age prediction [29% improvement] versus +0.7±12.1% of age prediction; P<0.001), and the RAND-36 physical measures of role functioning (P<0.01), physical functioning (P<0.01), energy/fatigue levels (P=0.01), and general health (P=0.03) and mental measure of pain scale (P=0.04). The renal rehabilitation exercise regimen was generally well tolerated.

Conclusions

A 12-week/24-session renal rehabilitation exercise program improved physical capacity and quality of life in patients with CKD stages 3 and 4. Longer follow-up is needed to determine if these findings will translate into decreased mortality rates.     

Apolipoprotein A-V variant (T-1131>C) affects plasma levels of non-high-density lipoprotein cholesterol in Caucasians

BACKGROUND

The importance of apolipoprotein A-V (APOAV) gene variants in the determination of plasma triglyceride levels in humans has been proven in several population studies.

OBJECTIVES

To investigate whether APOAV gene variants are associated with the different plasma cholesterol fractions.

METHODS

The influence of APOAV polymorphisms (T-1131>C, Ser19>Trp and Val153>Met) on plasma cholesterol fractions was evaluated in 1191 men and 1368 women representatively selected from the Czech population. Low-density lipoprotein cholesterol, non-high-density lipoprotein (non-HDL) cholesterol and HDL cholesterol levels were analyzed.

RESULTS

The T-1131>C variation in the APOAV gene was found to affect plasma non-HDL cholesterol, showing significantly higher levels in C-1131 carriers than in T/T-1131 homozygotes. This association was observed in both men (4.61±1.09 mmol/L in C-1131 carriers versus 4.47±1.07 mmol/L in T/T-1131 homozygotes; P<0.01) and women (4.46±1.22 mmol/L in C-1131 carriers versus 4.24±1.17 mmol/L in T/T-1131 homozygotes; P<0.01). Interestingly, when low-density lipoprotein cholesterol (obtained by the Friedewald formula) or HDL cholesterol levels were analyzed, no significant association was detected.

CONCLUSION

The APOAV gene variant T-1131>C may play a role not just in the genetic determination of triglyceride levels but may also influence plasma levels of non-HDL cholesterol.     

Yacon diet (Smallanthus sonchifolius,Asteraceae) improves hepatic insulin resistance via reducing Trb3 expression in Zucker fa/fa rats

Objective:

Yacon is a perennial plant forming a clump of >20 big, edible underground tubers. Yacon, which originates from South America, has become increasingly popular in the Japanese diet for tubers have a lower caloric value and a high fiber content. Recent studies have suggested that yacon feeding ameliorates diabetes as indicated by reduced blood glucose.

Methods:

We fed male Zucker fa/fa rats for 5 weeks with isocaloric normal chow diet containing from 6.5% control aroid or 6.5% yacon. Insulin sensitivity was evaluated by euglycemic-hyperinsulinemic clamp study.

Results:

Body weight was comparable between yacon- and aroid-fed rats. In the basal state, yacon feeding had an effect to lower fasting glucose levels from 184.1±4.1 to 167.8±2.7 mg dl⁻¹ (P<0.01), as well as basal hepatic glucose output (HGO) from 9.9±0.4 to 7.4 ± 0.2 mg kg⁻¹ per min (P<0.01). During the clamp studies, the glucose infusion rate required to maintain euglycemia was increased by 12.3% in yacon-fed rat. The insulin suppression of HGO was also increased in yacon-fed rats compared with control rats (85.3±2.4% vs 77.0±3.0% P<0.05), whereas the glucose disposal rate was not different between the two groups. Consistent with the clamp data, the insulin-stimulated phosphorylation of Akt was significantly enhanced in liver but not in skeletal muscle. Furthermore, tribbles 3 (Trb3) expression, which is a negative regulator of Akt activity, was markedly reduced in the liver of yacon-fed rats compared with control rats.

Conclusion:

These results indicate that the effect of yacon feeding to reduce blood glucose is likely due to its beneficial effects on hepatic insulin sensitivity in the insulin resistant state.     

A Comparison of Radiation Dose Between Standard and 3D Angiography in Congenital Heart Disease

Background

The use of three-dimensional rotational angiography (3D-RA) to assess patients with congenital heart diseases appears to be a promising technique despite the scarce literature available.

Objectives

The objective of this study was to describe our initial experience with 3D-RA and to compare its radiation dose to that of standard two-dimensional angiography (2D-SA).

Methods

Between September 2011 and April 2012, 18 patients underwent simultaneous 3D-RA and 2D-SA during diagnostic cardiac catheterization. Radiation dose was assessed using the dose-area-product (DAP).

Results

The median patient age and weight were 12.5 years and 47.5 Kg, respectively. The median DAP of each 3D-RA acquisition was 1093µGy.m² and 190µGy.m² for each 2D-SA acquisition (p<0.01). In patients weighing more than 45Kg (n=7), this difference was attenuated but still significant (1525 µGy.m² vs.413µGy.m², p=0.01). No difference was found between one 3D-RA and three 2D-SA (1525µGy.m² vs.1238 µGy.m², p = 0.575) in this population. This difference was significantly higher in patients weighing less than 45Kg (n=9) (713µGy.m² vs.81µGy.m², P = 0.008), even when comparing one 3D-RA with three 2D-SA (242µGy.m², respectively, p<0.008). 3D-RA was extremely useful for the assessment of conduits of univentricular hearts, tortuous branches of the pulmonary artery, and aorta relative to 2D-SA acquisitions.

Conclusions

The radiation dose of 3D-RA used in our institution was higher than those previously reported in the literature and this difference was more evident in children. This type of assessment is of paramount importance when starting to perform 3D-RA.     

Low-Dose Rapamycin (Sirolimus) Effects in Autosomal Dominant Polycystic Kidney Disease: An Open-Label Randomized Controlled Pilot Study

Background and objectives

The two largest studies of mammalian target of rapamycin inhibitor treatment of autosomal dominant polycystic kidney disease (ADPKD) demonstrated no clear benefit on the primary endpoint of total kidney volume (TKV) or on eGFR. The present study evaluated two levels of rapamycin on the 12-month change in ¹²⁵I-iothalamate GFR (iGFR) as the primary endpoint and TKV secondarily.

Design, setting, participants, & measurements

In a 12-month open-label pilot study, 30 adult patients with ADPKD were randomly assigned to low-dose (LD) rapamycin (rapamycin trough blood level, 2–5 ng/ml) (LD group, n=10), standard-dose (STD) rapamycin trough level (>5–8 ng/ml) (STD group, n=10), or standard care (SC group, n=10). They were evaluated with iGFR and noncontrast computed tomography.

Results

Change in iGFR at 12 months was significantly higher in the LD group (7.7±12.5 ml/min per 1.73 m²; n=9) than in the SC group (−11.2±9.1 ml/min per 1.73 m²; n=9) (LD versus SC: P<0.01). Change in iGFR at 12 months in the STD group (1.6±12.1 ml/min per 1.73 m²; n=8) was not significantly greater than that in the SC group (P=0.07), but it was in the combined treatment groups (LD+STD versus SC: P<0.01). Neither eGFR calculated by the CKD-Epidemiology Collaboration equation nor TKV (secondary endpoint) changed significantly from baseline to 12 months in any of the groups. On the basis of results of the mixed model, during the study, patients in the LD group had significantly lower trough blood levels of rapamycin (mean range±SD, 2.40±0.64 to 2.90±1.20 ng/ml) compared with those in the STD group (3.93±2.27 to 5.77±1.06 ng/ml) (P<0.01).

Conclusion

Patients with ADPKD receiving LD rapamycin demonstrated a significant increase in iGFR compared with those receiving standard care, without a significant effect on TKV after 12 months.