Michela Zanetti

Evidence for Acute Stimulation of Fibrinogen Production by Glucagon in Humans

Fibrinogen, an acute-phase protein, and glucagon, a stress hormone, are often elevated in many conditions of physical and metabolic stress, including uncontrolled diabetes. However, the possible mechanisms for this association are poorly known. We have studied the acute effects of selective hyperglucagonemia (raised from ∼200 to ∼350 pg/ml for 3 h) on fibrinogen fractional secretion rate (FSR) in eight normal subjects during infusion of somatostatin and replacement doses of insulin, glucagon, and growth hormone. Fibrinogen FSR was evaluated by precursor-product relationships using either Phe (n = 8) or Leu (n = 2) tracers. Hyperglucagonemia did not change either plasma Phe or Tyr specific activity. After hyperglucagonemia, fibrinogen FSR increased by ∼65% (from 12.9 ± 3.6 to 21.5 ± 6.1% per day, P < 0.025) using plasma Phe specific activity as the precursor pool. FSR increased by ∼80% (from 16.6 ± 4.8 to 29.4 ± 8.8% per day, P < 0.025) if plasma Phe specific activity was corrected for the ketoisocaproate/Leu enrichment (or specific activity) ratio to obtain an approximate estimate of intrahepatic Phe specific activity. FSR increased by ∼60% when using plasma Tyr specific activity as precursor pool (n = 8) (P < 0.05), as well as when using the Leu tracer precursorproduct relationship (n = 2). In conclusion, selective hyperglucagonemia for ∼3 h acutely stimulated fibrinogen FSR using a Phe tracer method. Thus, glucagon may be involved in the increase of fibrinogen concentration and FSR observed under stressed or pathologic conditions.

Protein metabolism in glucagonoma

Summary Although protein wasting and reduced amino acid concentrations are common findings in glucagonoma patients, the mechanisms underlying these alterations are unclear. Therefore, we studied basal postabsorptive leucine, phenylalanine and tyrosine turnover following L-[D3]-Leucine, L-[D5]-Phenylalanine and L-[D2]-Tyrosine i. v. infusions in one male and one female patient with glucagonoma, compared with healthy control volunteers. Plasma amino acid concentrations were reduced (–40 to 80 %, δ > 2 SD vs control subjects) in both patients. Plasma leucine, phenylalanine and tyrosine rates of appearance in patients with glucagonoma were similar to values in the control subjects, except leucine rate of appearence in the female patient with glucagonoma ( + &30 %, d > 2 SD). In contrast, the intracellular leucine rate of appearence, reflecting protein degradation, was considerably increased in both patients ( + 60–80 %, δ > 2 SD). Phenylalanine hydroxylation was moderately higher only in the male patient with glucagonoma ( + &30 %, d > 2 SD). Leucine, phenylalanine and tyrosine clearances ( + 100–300 %), as well as phenylalanine hydroxylative clearance ( + 75–100 %) were also increased in the patients. In conclusion, whole-body protein breakdown is enhanced in patients with glucagonoma compared with healthy control subjects. Phenylalanine hydroxylative clearance is also higher. Reduced plasma amino acid concentrations are probably due, at least in part, to their increased clearance. These alterations could contribute to the determination of the catabolic state of the glucagonoma syndrome. [Diabetologia (1999) 42: 326–329]

Differences in Estimates of Forearm Protein Synthesis Between Leucine and Phenylalanine Tracers Following Unbalanced Amino Acid Infusion

We compared the leucine (Leu) and phenylalanine (Phe) tracer-determined response of forearm protein synthesis (PS) before and after stimulation of protein anabolism by intravenous infusion of Leu-enriched, Phe-deficient amino acids and insulin (increased to approximately 100 microU/mL) with the euglycemic clamp. Six healthy subjects received primed-constant infusions of L-[ring-2H5]-Phe and L-[1-(14)C]-Leu, and steady-state forearm Phe and Leu kinetics were determined. Following the combined infusion, the arterial Leu concentration increased approximately 70% (P < .001), whereas Phe decreased about 15% (P < .01). Forearm PS and net balance (NB) increased (P < .05 or less v basal) using both amino acid tracers. However, the relative increments observed with the Leu tracer were more than 75% larger (P < .05 or less) than those observed with the Phe tracer, even when the data were corrected for the standard relative abundance of these two amino acids in forearm protein(s). Thus, the calculated changes of forearm PS and NB in response to an unbalanced amino acid infusion with hyperinsulinemia were affected by the plasma level of leucine and phenylalanine, whose tracers were used to estimate forearm protein turnover. Since these two essential amino acids share the same transport system, a competition at this level cannot be excluded.

Relationships between phenylalanine hydroxylation and plasma aromatic amino acid concentrations in humans

We investigated the relationships between phenylalanine hydroxylation (Phe Hy) and plasma concentrations of phenylalanine, tyrosine, and glucagon in healthy male volunteers (N = 13; age, 29 +/- 3 years). Phe Hy, as well as the Phe and Tyr rate of appearance (Ra), were measured during L-[2H5]-Phe and L-[2H2]-Tyr continuous intravenous (i.v.) infusions both under basal postabsorptive conditions (N = 13) and following divergent changes of plasma aromatic amino acids (AAA) concentrations. Namely, AAA were increased by administration of a balanced synthetic mixed meal (n = 6) or selectively decreased by i.v. infusion of insulin along with a Phe-deficient, Tyr and tryptophan-deprived amino acid mixture ([IAA] n = 7). Following the meal, plasma Phe (54 +/- 3 to 81 +/- 12 micromol/L), plasma Tyr (54 +/- 4 to 91 +/- 7), Phe Hy (0.09 +/- 0.01 to 0.15 +/- 0.02 micromol/kg x min), Phe Ra (0.65 +/- 0.04 to 0.96 +/- 0.07), and Tyr Ra (0.51 +/- 0.03 to 0.93 +/- 0.11) all significantly increased (P < or = .05 v basal). IAA infusion significantly decreased plasma Phe (to 47 +/- 3 micromol/L), plasma Tyr (to 25 +/- 4), Phe Hy (to 0.07 +/- 0.004 micromol/kg x min), and Tyr Ra (to 0.29 +/- 0.02; all P < or = .05 v sal), while Phe Ra did not change (0.64 +/- 0.04, NS). Plasma glucagon did not change in the three experimental periods (basal, 85 +/- 7; meal, 72 +/- 10; IAA, 92 +/- 14 pg/mL; NS). Using linear regression analysis, plasma Phe was positively related to both Phe Hy (R2 = .76, P < .001) and plasma Tyr (R2 = .80, P < .001); Phe Hy and plasma Tyr were also significantly correlated (R2 = .60, P < .001). No correlation was found between Phe Hy and basal plasma glucagon (R2 = .04, NS). Using multiple regression analysis with plasma Tyr as the dependent variable, plasma Phe was still correlation with plasma Tyr (t = 4.29, P = .0002), while the relationship between Phe Hy and plasma Tyr was no longer significant (t = 0.69, P = .49). These data indicate that plasma Phe is closely associated with its own hydroxylative disposal in humans, and confirm that Phe conversion to Tyr may play a physiological role in maintaining balanced plasma phenylalanine and tyrosine concentrations.

Insulin infusion normalizes fasting and post‐prandial albumin and fibrinogen synthesis in Type 1 diabetes mellitus

Aims  The effect of metabolic control on hepatic synthesis of plasma proteins in Type 1 diabetes mellitus (T1DM), in the post‐absorptive and post‐prandial state, is not known.

The Global Warming Potential of Building Materials: An Application of Life Cycle Analysis in Nepal

This paper analyzes the global-warming potential of materials used to construct the walls of 3 building types—traditional, semimodern, and modern—in Sagarmatha National Park and Buffer Zone in Nepal, using the life-cycle assessment approach. Traditional buildings use local materials, mainly wood and stone, while semimodern and modern buildings use different amounts of commercial materials, such as cement and glass wool. A comparison of the greenhouse gas emissions associated with the 3 building types, using as the functional unit 1 m2 of wall, found that traditional buildings release about one-fourth of the greenhouse gas emissions released by semimodern buildings and less than one-fifth of the emissions of modern buildings. However, the use of thermal insulation in the modern building walls helps to reduce the energy consumption for space heating and consequently to reduce the global warming potential. In 25 years, the total global warming potential of a traditional building will be 20% higher than that of a modern building. If local materials, such as wood, are used in building construction, the emissions from production and transportation could be dramatically reduced.

Hybrid silane-crosslinking polymers: a potential alternative to polyurethane wood adhesives? A preliminary investigation by TMA

In the last years, the research on wood adhesives has focused on matching technical performance with low health and environmental impacts. This study presents the first development of a new adhesive technology based on hybrid silane-crosslinking polymers that can combine both silicone’s and polyurethane’s adhesive properties. The advantage of hybrid silane-crosslinking polymers is the absence of potential harmful chemicals, such as isocyanates and solvents. Two hybrid formulations were characterized by thermo-mechanical analysis (TMA) and glued wood product elasticity is discussed in this brief original.

Decreased VLDL-Apo B 100 Fractional Synthesis Rate Despite Hypertriglyceridemia in Subjects With Type 2 Diabetes and Nephropathy

CONTEXT Subjects with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) often exhibit hypertriglyceridemia. The mechanism(s) of such an increase are poorly known. OBJECTIVE We investigated very low-density lipoprotein (VLDL)-Apo B 100 kinetics in T2DM subjects with and without DN, and in healthy controls. DESIGN Stable isotope (13)C-leucine infusion and modeling analysis of tracer-to-tracee ratio dynamics in the protein product pool in the 6-8-h period following tracer infusion were employed. SETTING Male subjects affected by T2DM, either with (n = 9) or without (n = 5) DN, and healthy male controls (n = 6), were studied under spontaneous glycemic levels in the post-absorptive state. RESULTS In the T2DM patients with DN, plasma triglyceride (TG) (mean ± SD; 2.2 ± 0.8 mmol/L) and VLDL-Apo B 100 (17.4 ± 10.4 mg/dL) concentrations, and VLDL-Apo B 100 pool (0.56 ± 0.29 g), were ∼60-80% greater (P < .05 or less) than those of the T2DM subjects without DN (TG, 1.4 ± 0.5 mmol/L; VLDL-Apo B 100, 9.9 ± 2.5 mg/dL; VLDL-Apo B 100 pool, 0.36 ± 0.09 g), and ∼80-110% greater (P < .04 or less) than those of nondiabetic controls (TG, 1.2 ± 0.4 mmol/L; VLDL-Apo B 100, 8.2 ± 1.7 mg/dL; VLDL-Apo B 100, 0.32 ± 0.09 g). In sharp contrast however, in the subjects with T2DM and DN, VLDL-Apo B 100 fractional synthesis rate was ≥50% lower (4.8 ± 2.2 pools/d) than that of either the T2DM subjects without DN (9.9 ± 4.3 pools/d; P < .025) or the control subjects (12.5 ± 9.1 pools/d; P < .04). CONCLUSIONS The hypertriglyceridemia of T2DM patients with DN is not due to hepatic VLDL-Apo B 100 overproduction, which is decreased, but it should be attributed to decreased apolipoprotein removal.

Product environmental footprint of a cross-laminated timber system: a case study in Italy

PurposeThis study aims to apply the product environmental footprint (PEF) methodology to a wooden wall element, the Massiv–Holz–Mauer® (MHM), in an existing building in Northern Italy. The PEF is a multi-criteria measure of the environmental performance of products throughout their life cycle (European Commission 2013).MethodsThe environmental footprint of the MHM wall element was calculated for the impact categories required by the PEF, using a cradle-to-grave approach. Foreground data was collected at each life stage and completed using data from the Ecoinvent 3.1 database (Wernet et al. 2016). An additional analysis (optional according to the PEF methodology) was conducted for assessing the sustainability of forest management in the sites where wood is extracted from, using data from the forest management plan.Results and discussionThe results show that, for most of the environmental indicators, the use phase has the highest environmental impact, followed by the production, end-of-life, raw material acquisition, and construction phases. These results depend on the different duration of the life cycle phases, and on the attribution of the total operational energy of the building to the structural components of the wall, though other factors, such as the efficiency of the heating system, may be responsible. Future PEF sectorial specification should specify how to account for the use phase of structural building components. For the majority of the impact categories, the impact is mainly due to processes that occur in the background system, such as production of capital goods and construction of facilities and storehouses. The wooden material production generates relatively low impacts, thanks to the fact that the wood is sourced locally and from forests where a close-to-nature forest management is adopted, characterized by natural regeneration without the use of fertilizers and pesticides.ConclusionsThis study shows that the PEF methodology can be successfully applied to a single wood supply chain, allowing the identification of the main hotspots and actions for reducing the environmental impacts. The PEF leaves space for additional environmental information, which, for some product categories, may play an important role. In the case of wood products, we suggest the inclusion of an assessment, even qualitative, of the sustainability of forest management.

New insights into the psychological dimension of wood–human interaction

The effect a wooden-built environment exerts on the physical and psychological well-being of people has mostly been investigated by evaluation, through a limited number of sensory modalities, of small size stimuli. In this research, two real-size wooden and plaster indoor settings were used to examine the influence of wood on people’s emotions and perceptions. Three questionnaires assessed participants’ multimodal sensory, affective, and cognitive responses to the settings (Semantic Differential questionnaire), their emotional state (Positive and Negative Affect Schedule), and their environmental behaviour and biophilia degree (Nature Relatedness Scale). The results revealed that wood induces more positive emotions than plaster, and that individual biophilia degree appears to influence the tactile, auditory, and olfactory evaluation of the settings. It furthermore indicates how wood used in real buildings positively influences human psychological well-being and highlights the importance of considering multiple sensory modalities when investigating wood–human interaction.