The effects of carbohydrate variation in isocaloric diets on glycogenolysis and gluconeogenesis in healthy men

To evaluate the effect of dietary carbohydrate content on postabsorptive glucose metabolism, we quantified gluconeogenesis and glycogenolysis after 11 days of high carbohydrate (85% carbohydrate), control (44% carbohydrate), and very low carbohydrate (2% carbohydrate) diets in six healthy men. Diets were eucaloric and provided 15% of energy as protein. Postabsorptive glucose production was measured by infusion of [6,6-2H2]glucose, and fractional gluconeogenesis was measured by ingestion of 2H2O. Postabsorptive glucose production rates were 13.0 +/- 0.7, 11.4 +/- 0.4, and 9.7 +/- 0.4 micromol/kg x min after high carbohydrate, control, and very low carbohydrate diets, respectively (P < 0.001 among the three diets). Gluconeogenesis was about 14% higher after the very low carbohydrate diet (6.3 +/- 0.2 micromol/kg x min; P = 0.001) compared to the control diet, but was not different between the high carbohydrate and control diets (5.5 +/- 0.3 vs. 5.5 +/- 0.2 micromol/kg x min). The rates of glycogenolysis were 7.5 +/- 0.5, 5.9 +/- 0.3, and 3.4 +/- 0.3 micromol/kg x min, respectively (P < 0.001 among the three diets). We conclude that under eucaloric conditions in healthy subjects, dietary carbohydrate content affects the rate of postabsorptive glucose production mainly by modulation of glycogenolysis. In contrast, dietary carbohydrate content affects the postabsorptive rate of gluconeogenesis minimally, as evidenced by only a slight increase in gluconeogenesis during severe carbohydrate restriction.     

Introduction to the Special Issue on “Promoting a Culture of Prevention: an International Perspective”

Prevention Science - The primary goal of this special issue is to showcase novel, theory-driven, creative, and rigorous contributions to our understanding of the existence and development of a...     

Use of cell-free collagen type I matrix implants for the treatment of small cartilage defects in the knee: clinical and magnetic resonance imaging evaluation

Purpose

Articular cartilage defects of the knee are a common condition for which several repair techniques have been described. The aim of the present study was to assess medium-term results of a one-step procedure using a cell-free collagen type I matrix.

Methods

Fifteen patients with articular cartilage defects of the knee were treated with an 11-mm-diameter cell-free collagen type 1 matrix implant. The matrices were implanted in a press-fit manner into the defect after careful debridement down to the subchondral bone but without penetration of this margin. Follow-up examinations were carried out at 6 weeks, 6 months, and at 12, 24, 36, and 48 months after implantation. Clinical assessment included the visual analogue scale (VAS), the Tegner activity scale, and the International Knee Documentation Committee (IKDC) score. Radiological assessment for graft attachment and tissue regeneration was performed using the magnetic observation of cartilage repair tissue (MOCART) score.

Results

A total of 15 patients (males: n = 6 and females: n = 9) with a mean age of 26.4 years (range 19–40) were treated. The mean VAS improved significantly when compared to the preoperative values (P < 0.05). Six weeks after implantation, IKDC values were slightly lower than the preoperative values (n.s.), but increased significantly at final follow-up (P < 0.05). At 24 months, there were no significant differences in the median Tegner score between the post-operative values and the preoperative values (n.s.). However, after 36 months, a significant improvement was noted that lasted at least up to 48 months (P < 0.05). The MOCART score improved consistently up to 4 years after implantation, with significant improvements already observed after 12 months (P < 0.05). No correlation between the clinical scores and the MOCART score could be perceived.

Conclusion

The present study showed that the use of cell-free collagen type I matrix implants led to a significant and durable improvement in all the clinical and imaging scores investigated 4 years after implantation.

Level of evidence

IV.     

Arginine vasopressin does not alter mucosal tissue oxygen tension and oxygen supply in an acute endotoxemic pig model

Objective To determine the effects of increasing dosages of continuously infused arginine-vasopressin (AVP) on mucosal tissue oxygen tension and oxygen supply in an auto-perfused, innervated jejunal segment in an acute endotoxic porcine model.Design Prospective, randomized, experimental study.Setting University hospital animal research laboratory.Interventions Jejunal mucosal tissue PO₂ was measured employing two Clark-type surface oxygen electrodes. Oxygen saturation of jejunal microvascular hemoglobin was determined by tissue reflectance spectrophotometry. Systemic hemodynamic variables, mesenteric-venous and systemic acid base and blood gas variables and lactate measurements were recorded. Measurements were performed at baseline, after E. coli lipopolysaccharide (LPS) administration and at 20 min intervals during incremental AVP infusion ( n =8; 0.014, 0.029, 0.057, 0.114 and 0.229 IU kg^-1 h^-1, respectively) or infusion of saline ( n =8).Measurements and results LPS infusion leads to a significant ( P <0.05) decrease of mucosal tissue oxygen tension (PO₂muc, 24±3 to 12±2 mmHg) and microvascular hemoglobin oxygen saturation (HbO₂, 38±4 to 21±4%). Mesenteric venous lactate level increased (2.4±0.3 to 4.7±1.7 mmol l^-1), while mesenteric venous pH decreased (7.38±0.02 to 7.26±0.12), indicating tissue hypoxia. AVP significantly increased mean arterial pressure (MAP, 81±15 to 97±17 at 0.057 IU kg^-1 h^-1). No differences in jejunal mucosal oxygenation occurred between study groups at any dosage during the experimental protocol.Conclusion AVP administration did not further compromise mucosal tissue oxygen tension and oxygen supply in the acute phase of endotoxic pigs.This article refers to the editorial     

Total homocysteine, folate, and cobalamin, and their relation to genetic polymorphisms, lifestyle and body mass index in healthy children and adolescents

We investigated total homocysteine (tHcy) concentrations and relations between tHcy and folate, cobalamin (Cbl), genetic polymorphisms (MTHFR 677C > T, MTHFR 1298A > C, MTHFR 1793G > A), blood pressure (BP), body mass index (BMI), cholesterol, triglycerides, sports activities, family and individual history of cardiovascular disease (CVD) and lifestyle issues in 264 healthy children and adolescents (2-17 y). THcy concentrations significantly increased while folate and Cbl decreased with age without gender differences. Age, folate and Cbl were significant predictors for tHcy concentrations. THcy was higher but within normal ranges in MTHFR 677TT homozygotes (10.6%) and carriers of the MTHFR 1793A allele (8%). Only two individuals (0.8%), both with low tHcy concentrations, were homozygous for MTHFR 1793AA. THcy concentration correlated positively with creatinine, triglycerides, BMI and systolic BP and was not related to cholesterol, sports activities and family history of CVD. In conclusion, tHcy concentrations in this pediatric population were significantly influenced by age, folate and Cbl concentrations. No gender differences for tHcy, folate or Cbl concentrations were observed. Both the MTHFR 677TT genotype and the MTHFR 1793A allele were not associated with hyperhomocysteinemia. The prevalence of the MTHFR 1793AA genotype was too low for meaningful interpretation.     

Growth hormone blunts protein oxidation and promotes protein turnover to a similar extent in abdominally obese and normal-weight women

Abdominally obese individuals have reduced 24-h plasma GH concentrations. Their normal plasma IGF-I levels may reflect GH hypersensitivity. Alternatively, obesity-associated hyposomatotropism may cause less biological effect in target tissues. We therefore determined whole-body responsiveness to the anabolic effects of GH in abdominally obese (OB) and normal weight (NW) premenopausal women. A 1-h iv infusion of GH or placebo was randomly administered to six NW (body mass index, 21.1 +/- 1.9 kg/m(2)) and six OB (body mass index, 35.5 +/- 1.5 kg/m(2)) women in a cross-over design. Endogenous insulin, glucagon and GH secretion was suppressed by infusion of somatostatin. Whole-body protein turnover was measured using a 10-h infusion of [(13)C]-leucine. GH administration induced a similar plasma GH peak in NW and OB women (49.8 +/- 10.4 vs. 45.1 +/- 5.6 mU/liter). GH, compared with placebo infusion, increased nonoxidative leucine disposal, P < 0.0001) and endogenous leucine appearance (R(a), P = 0.0004) but decreased leucine oxidation (P = 0.0051). All changes were similar in both groups. Accordingly, whole-body GH responsiveness, defined as the maximum response of nonoxidative leucine disposal, leucine R(a), and oxidation per unit of GH, was not different in OB and NW women (0.25 +/- 0.18 vs. 0.19 +/- 0.17 micro mol/kg.h, 0.21 +/- 0.23 vs. 0.13 +/- 0.17 micro mol/kg.h, and -0.10 +/- 0.08 vs. -0.08 +/- 0.05 micro mol/kg.h, respectively). These results indicated that whole-body tissue responsiveness to the net anabolic effect of GH is similar in OB and NW women. Hence, we inferred that hyposomatotropism may promote amino acid oxidation and blunt protein turnover in abdominal obesity. However, hyposomatotropism cannot account for all anomalous features of protein metabolism in abdominally obese humans.     

Hypocretin deficiency in narcoleptic humans is associated with abdominal obesity

OBJECTIVE: To determine the prevalence of obesity among patients with narcolepsy, to estimate associated long-term health risks on the basis of waist circumference, and to distinguish the impact of hypocretin deficiency from that of increased daytime sleepiness (i.e., reduced physical activity) on these anthropometric measures. RESEARCH METHODS AND PROCEDURES: A cross-sectional, case-control study was conducted. Patients with narcolepsy (n = 138) or idiopathic hypersomnia (IH) (n = 33) were included. Age-matched, healthy members of the Dutch population (Monitoring Project on Risk Factors for Chronic Diseases and Doetinchem Project; n = 10,526) were used as controls. BMI and waist circumference were determined. RESULTS: Obesity (BMI > or = 30 kg/m(2)) and overweight (BMI 25 to 30 kg/m(2)) occurred more often among narcolepsy patients [prevalence: 33% (narcoleptics) vs. 12.5% (controls) and 43% (narcoleptics) vs. 36% (controls), respectively; both p < 0.05]. Narcoleptics had a larger waist circumference (mean difference 5 +/- 1.4 cm, p < 0.001). The BMI of patients with IH was significantly lower than that of narcolepsy patients (25.6 +/- 3.6 vs. 28.5 +/- 5.4 kg/m(2); p = 0.004). DISCUSSION: Overweight and obesity occur frequently in patients with narcolepsy. Moreover, these patients have an increased waist circumference, indicating excess fat storage in abdominal depots. The fact that patients with IH had a lower BMI than narcoleptics supports the notion that excessive daytime sleepiness (i.e., inactivity) cannot account for excess body fat in narcoleptic patients.     

Eotaxin-2, a Novel CC Chemokine that Is Selective for the Chemokine Receptor CCR3, and Acts Like Eotaxin on Human Eosinophil and Basophil Leukocytes

A novel human CC chemokine consisting of 78 amino acids and having a molecular mass of 8,778.3 daltons (VVIPSPCCMF FVSKRIPENR VVSYQLSSRS TCLKAGVIFT TKKGQQ SCGD PKQEWVQRYM KNLDAKQKKA SPRARAVA) was isolated together with three minor COOH-terminally truncated variants with 73, 75, and 76 residues. The new chemokine was termed eotaxin-2 because it is functionally very similar to eotaxin. In terms of structure, however, eotaxin and eotaxin-2 are rather distant, they share only 39% identical amino acids and differ almost completely in the NH₂-terminal region. Eotaxin-2 induced chemotaxis of eosinophils as well as basophils, with a typically bimodal concentration dependence, and the release of histamine and leukotriene C₄ from basophils that had been primed with IL-3. In all assays, eotaxin-2 had the same efficacy as eotaxin, but was somewhat less potent. The migration and the release responses were abrogated in the presence of a monoclonal antibody that selectively blocks the eotaxin receptor, CCR3, indicating that eotaxin-2, like eotaxin, acts exclusively via CCR3. Receptor usage was also studied in desensitization experiments by measuring [Ca²⁺]_i changes in eosinophils. Complete cross-desensitization was observed between eotaxin-2, eotaxin and MCP-4 confirming activation via CCR3. No Ca²⁺ mobilization was obtained in neutrophils, monocytes and lymphocytes, in agreement with the lack of chemotactic responsiveness. Intradermal injection of eotaxin-2 in a rhesus monkey (100 or 1,000 pmol per site) induced a marked local infiltration of eosinophils, which was most pronounced in the vicinity of postcapillary venules and was comparable to the effect of eotaxin.