Diet/Exercise versus pioglitazone: effects of insulin sensitization with decreasing or increasing fat mass on adipokines and inflammatory markers

BACKGROUND: Plasma adipokine concentrations are variably related to fatness/insulin resistance and may act via endocrine mechanisms. We assessed the relationship among plasma adipokine concentrations and their relationship with insulin sensitivity and body composition in obese adults before and after insulin sensitization accomplished using diet/exercise or pioglitazone. METHODS: Plasma adipokine concentrations, insulin sensitivity, and body composition were assessed in 39 upper-body obese insulin-resistant, nondiabetic adults before and after 19 wk of diet/exercise or 30 mg/d pioglitazone. RESULTS: Diet/exercise reduced body fat and visceral fat and improved insulin sensitivity parameters; pioglitazone improved insulin sensitivity to a similar degree but increased body fat. Adiponectin increased more after pioglitazone (4770 +/- 487 vs. 8351 +/- 693.6 ng/ml, P < 0.001) than after diet/exercise (4704 +/- 367 to 5426 +/- 325.3 ng/ml, P < 0.01), whereas TNFalpha, IL-6, and resistin did not change. C-reactive protein decreased with diet/exercise. Adipokine concentrations were not correlated with each other at baseline or after insulin sensitization, except TNFalpha and IL-6 (r = 0.43, P < 0.05); IL-6 was inversely correlated with resistin. Only adiponectin was correlated (P < 0.05) with indices of insulin sensitivity. Adiponectin concentrations were inversely correlated with visceral fat and with sc fat depots in men but positively correlated with sc fat in women. CONCLUSION: Plasma adipokine concentrations were not consistently interrelated, and only adiponectin displayed the expected relationship with insulin sensitivity and sensitization. These findings do not support an endocrine role for resistin, TNFalpha, and IL-6 in mediating changes in insulin resistance after diet/exercise or pioglitazone.     

Preparation and anticoagulant activity of the phosphosulfomannan PI-88

A yeast-derived phosphomannan mixture was chemically sulfonated and the composition and structure of the product mixture was studied. This phosphosulfomannan mixture, PI-88, is currently under clinical evaluation as an anti-cancer agent. Analysis using capillary electrophoresis demonstrated that PI-88 was a multi-component mixture. Gel permeation chromatography provided four fractions of PI-88 that contained components which differed in size from disaccharide to hexasaccharide, and by degree of sulfation. These fractions were characterised by spectroscopic and chromatographic methods and the structure of PI-88 is that expected based on the structure of the phosphomannan starting material. The anticoagulant activity of these fractions was evaluated and the structural requirements for activity are described.     

Effects of deferoxamine, a chelator of free iron, on NA(+), K(+)-ATPase activity of cortical brain cell membrane during early reperfusion after hypoxia-ischemia in newborn lambs

Free iron chelation after hypoxia-ischemia can reduce free radical-induced damage to brain cell membranes and preserve electrical brain activity. We investigated whether chelation of free iron with deferoxamine (DFO) preserved cortical cell membrane activity of Na(+),K(+)-ATPase and electrocortical brain activity (ECBA) of newborn lambs during early reperfusion after severe hypoxia-ischemia. Hypoxia was induced in 16 lambs by decreasing the fraction of inspired oxygen to 0.07 for 30 min, followed by a 5-min period of hypotension (mean arterial blood pressure <35 mm Hg). ECBA (in microvolts) was measured using a cerebral function monitor. Immediately after hypoxia and additional ischemia, eight lambs received DFO (2.5 mg/kg, i.v.), and seven lambs received a placebo (PLAC). Two lambs underwent sham operation. One hundred eighty minutes after completion of hypoxia and ischemia, the brains were obtained and frozen. Na(+),K(+)-ATPase activity was measured in the P(2) fraction of cortical tissue. Na(+),K(+)-ATPase activity was 35.1 +/- 7.4, 42.0 +/- 7.6, and 40.7 +/- 1.4 micromol inorganic phosphate/mg protein per hour in PLAC-treated, DFO-treated, and sham-operated lambs, respectively (p < 0.05: DFO versus PLAC). ECBA was 11.2 +/- 6.1, 14.8 +/- 4.8, and 17.5+/-.0.5 microV in PLAC-treated, DFO-treated, and sham-operated lambs, respectively (p = 0.06: DFO versus PLAC). Na(+),K(+)-ATPase activity correlated with ECBA at 180 min of reperfusion (r = 0.85, p < 0.001). We conclude that Na(+),K(+)-ATPase activity of cortical brain tissue was higher in DFO-treated lambs compared with PLAC-treated animals during the early reperfusion phase after severe hypoxia-ischemia, suggesting a reduction of free radical formation by DFO. Furthermore, a positive relationship was found between Na(+),K(+)-ATPase activity and ECBA.     

Effects of fish-oil and folate supplementation of pregnant women on maternal and fetal plasma concentrations of docosahexaenoic acid and eicosapentaenoic acid: a European randomized multicenter trial

BACKGROUND: Pregnant women usually meet their increased energy needs but do not always meet their increased micronutrient requirements. The supply of both folic acid and docosahexaenoic acid (DHA) has been related to positive pregnancy and infant outcomes. OBJECTIVE: We aimed to assess whether fish-oil (FO) supplementation with or without folate from gestation week 22 to birth improves maternal and fetal n-3 long-chain polyunsaturated fatty acid (n-3 LC-PUFA) status. DESIGN: We conducted a multicenter (Germany, Hungary, and Spain), randomized, double-blind, 2 x 2 factorial, placebo-controlled trial. From gestation week 22 until delivery, 311 pregnant women received daily a preparation with FO [0.5 g DHA and 0.15 g eicosapentaenoic acid (EPA)], 400 microg methyltetrahydrofolic acid (MTHF), FO with MTHF, or placebo. Outcome measures included maternal and cord plasma DHA and EPA contents at gestation weeks 20 and 30 and at delivery, indicators of pregnancy outcome, and fetal development. RESULTS: FO significantly (P<0.001) increased maternal DHA and EPA (% by wt), as shown by 3-factor repeated-measures ANOVA (ie, MTHF, FO, and time) with adjustment for maternal baseline DHA and EPA. In addition, FO significantly (P<0.001) increased cord blood DHA (% by wt; 2-factor ANOVA). MTHF was significantly (P=0.046) associated with increased maternal DHA (% by wt). There was no FO x MTHF interaction for the time course of DHA or EPA (P=0.927 and 0.893). Pregnancy outcomes and fetal development did not differ significantly among the intervention groups. CONCLUSIONS: FO supplementation from gestation week 22 until delivery improves fetal n-3 LC-PUFA status and attenuates depletion of maternal stores. MTHF may further enhance maternal n-3 LC-PUFA proportions.     

Effect of an occlusal screw-access hole on the fracture resistance of permanently cemented implant crowns: a laboratory study

This study aimed to evaluate the fracture resistance of cement-retained metal-ceramic implant-supported posterior crowns. Three groups of 10 restorations each were tested: group A (cement-retained using zinc phosphate), group B (cement-retained using zinc oxide-eugenol), and group C (cement-retained using zinc phosphate but with an occlusal screw-access hole). All specimens were thermocycled and vertically loaded in a universal testing machine. Mean values of fracture loads were calculated and analyzed statistically. The cement-retained restorations without an occlusal screw-access hole showed significantly higher mean fracture loads than those having one. The type of cement did not affect the porcelain fracture resistance significantly.     

Porcelain Fracture Resistance of Screw‐Retained,Cement‐Retained,and Screw‐Cement‐Retained Implant‐Supported Metal Ceramic Posterior Crowns

Purpose: The purpose of this in vitro study was to compare the porcelain fracture resistance between screw‐retained, cement‐retained, and combined screw‐ and cement‐retained metal–ceramic (MC) implant‐supported posterior single crowns; and to investigate the effect of offsetting the occlusal screw‐access opening on porcelain fracture resistance of screw‐retained and cement‐retained MC implant‐supported posterior single crowns. Materials and Methods: Forty standardized MC molar‐shaped restorations were fabricated. The 40 restorations were divided into four groups (SRC, SRO, CRP, and CSC) of 10 specimens each. Group SRC: screw‐retained, screw‐access hole placed in the center of the occlusal surface; Group SRO: screw‐retained, screw access hole placed 1 mm offset from the center of the occlusal surface toward the buccal cusp; Group CRP: cement‐retained, zinc phosphate cement was used; Group CSC: cement‐retained with a screw‐access hole in the center of the occlusal surface. The screw‐retained restorations and abutments were directly attached to 3i implant fixtures embedded in acrylic resin blocks. Subsequently, all test specimens were thermocycled and vertically loaded in a universal testing machine at a crosshead speed of 2 mm/min until fracture. Mean values of load at fracture (in N) were calculated in each group and compared with a one‐way ANOVA and Tukey's Studentized test (α= 0.05). Results: Mean values of loads required to fracture the restorations were as follows (N): Group SRC: 1721 ± 593; Group SRO: 1885 ± 491; Group CRP: 3707 ± 1086; Group CSC: 1700 ± 526. Groups SRC, SRO, and CSC required a significantly lower force to fracture the porcelain than did the CRP group (p < 0.05). Conclusion: The cement‐retained restorations showed significantly higher mean fracture loads than the restorations having screw‐access openings in their occlusal surface. The position of the screw‐access hole within the occlusal surface did not significantly affect the porcelain fracture resistance.     

Influence of inhibition of nitric oxide synthesis on cardiac function in the newborn lamb after hypoxic-ischemic injury

The aim of the present study was to investigate the effect of immediate post-hypoxic-ischemic (HI) inhibition of nitric oxide synthesis by N(omega)-nitro-L-arginine (NLA) on cardiac function and reactive oxygen species production. Fifteen newborn lambs were subjected to severe HI. Upon resuscitation 5 received 10 mg NLA/kg, 4 40 mg NLA/kg and 6 a placebo. Left ventricular (LV) contractility, cardiac output (CO), non-protein-bound iron (NPBI), ratio of reduced/oxidized ascorbic acid, alpha-tocopherol, sulfhydryl groups and malondialdehyde were measured before and 15, 60 and 120 min after resuscitation. There was a significant decrease in CO in all 3 groups at 60 min post-HI (p < 0.05). Reactive oxygen species production was also highest at 60 min post-HI (significantly increased NPBI and decrease in sulfhydryl groups in control lambs; p < 0.05). These results suggest neither a positive nor a negative effect of nitric oxide synthesis inhibition on post-HI myocardial performance but may suggest a positive effect of NLA on reactive oxygen species-mediated post-HI damage.     

Effects of pioglitazone versus diet and exercise on metabolic health and fat distribution in upper body obesity

OBJECTIVE: Insulin resistance is associated with visceral adiposity, and interventions that reduce this depot, e.g., diet and exercise, improve insulin resistance. Thiazolidinediones (TZDs) also improve insulin action but paradoxically increase total fat mass, perhaps through remodeling (recruitment of smaller fat cells) and redistribution of adipose tissue. We assessed the effects of pioglitazone versus diet and exercise on fat distribution and the relationship between fat distribution and insulin sensitivity in upper body obesity. RESEARCH DESIGN AND METHODS: Thirty-nine upper body obese, insulin-resistant, nondiabetic men and premenopausal women were randomly assigned to receive either 30 mg/day pioglitazone or a diet and exercise program for 20 weeks. Before and after the intervention, insulin sensitivity, body composition, body fat distribution (waist-to-hip ratio [WHR], computed tomography abdomen, and dual-energy X-ray absorptiometry), and abdominal and femoral fat cell size were assessed. RESULTS: Diet and exercise resulted in an 11.8 +/- 1.1 kg weight loss. Both diet and exercise and pioglitazone improved insulin sensitivity, but only the former was associated with loss of intra-abdominal fat. Pioglitazone increased total body fat, which preferentially accumulated in the lower body depot in both men and women. WHRs decreased in both groups. Abdominal fat cell size decreased (P = 0.06) after diet and exercise. No statistically significant changes in fat cell size were observed in pioglitazone-treated volunteers. CONCLUSIONS: In nondiabetic upper body obese subjects, increasing insulin sensitivity via diet and exercise accompanies reductions in visceral fat. Pioglitazone treatment also improves insulin sensitivity and lowers WHR, but this is due to a selective increase in lower body fat. This confirms a site-specific responsiveness of adipose tissue to TZD and suggests that improvements in insulin sensitivity by pioglitazone are achieved independent of changes in intra-abdominal fat.     

Acute Effects of Cocoa Flavanols on Blood Pressure and Peripheral Vascular Reactivity in Type 2 Diabetes Mellitus and Essential Hypertension

Background: Type 2 diabetes mellitus (T2DM) is associated with a high risk of vascular complications. Interestingly, cocoa flavanols (CF) can exert beneficial vascular effects in non-diabetic subjects. However, these effects have only been scarcely studied in T2DM. Therefore, we performed a study to assess the effects on vascular reactivity of a single dose of CF (790 mg) in T2DM and whether certain antihypertensive drugs may modulate these effects. Methods: 24 non-diabetic and 11 T2DM subjects were studied in a cross-over design. Fasting blood samples, blood pressure (BP), and arterial vasoreactivity (flow-mediated dilation) were assessed before and 70 min after capsule ingestion. Muscle microvascular reactivity was only assessed after capsule ingestion. Age, waist-to-hip ratio, BP at baseline, and the use of antihypertensive drugs were regarded as covariates in a mixed models analysis. Results: CF ingestion did not affect any parameter. However, independent of the type of capsules ingested, a decrease in diastolic BP by 3 mmHg (95% CI: −4.0; −2.0) and an increase in the change in brachial artery diameter (pre vs. post occlusion) by 0.06 mm (95% CI: 0.01; 0.12) were detected in the non-diabetic group, while they remained unchanged in the T2DM group. Conclusion: No beneficial effects of CF were detected on vascular reactivity parameters in T2DM and non-diabetic participants.