Dog bites man or man bites dog? The enigma of the amino acid conjugations.

The proposition posed is that the value of amino acid conjugation to the organism is not, as in the traditional view, to use amino acids for the detoxication of aromatic acids. Rather, the converse is more likely, to use aromatic acids that originate from the diet and gut microbiota to assist in the regulation of body stores of amino acids, such as glycine, glutamate, and, in certain invertebrates, arginine, that are key neurotransmitters in the central nervous system (CNS). As such, the amino acid conjugations are not so much detoxication reactions, rather they are homeostatic and neuroregulatory processes. Experimental data have been culled in support of this hypothesis from a broad range of scientific and clinical literature. Such data include the low detoxication value of amino acid conjugations and the Janus nature of certain amino acids that are both neurotransmitters and apparent conjugating agents. Amino acid scavenging mechanisms in blood deplete brain amino acids. Amino acids glutamate and glycine when trafficked from brain are metabolized to conjugates of aromatic acids in hepatic mitochondria and then irreversibly excreted into urine. This process is used clinically to deplete excess nitrogen in cases of urea cycle enzymopathies through excretion of glycine or glutamine as their aromatic acid conjugates. Untoward effects of high-dose phenylacetic acid surround CNS toxicity. There appears to be a relationship between extent of glycine scavenging by benzoic acid and psychomotor function. Glycine and glutamine scavenging by conjugation with aromatic acids may have important psychosomatic consequences that link diet to health, wellbeing, and disease.

Long-term microtensile bond strength of surface modified zirconia.

OBJECTIVE: To compare long-term microtensile bond strength of zirconia, surface-modified via a novel treatment, to current surface conditioning methods for zirconia, when resin bonded to dental composite. METHODS: Two ProCAD (porcelain) and 10 sintered ZirCAD (ZrO(2)) blocks (18 mm × 14 mm × 12 mm) were obtained from manufacturers. Twelve Herculite XRV composite blocks were fabricated (18 mm × 14 mm × 12 mm). Bonding surface of blocks was polished through 1200-grit SiC and air-abraded (50 µm alumina, 0.28MPa, 20s). Blocks were then separated into six groups: (1) porcelain (control), HF-etched/silane-treated, (2) ZrO(2), tribochemical-coated/silane-treated, (3) ZrO(2), primer-treated, (4) ZrO(2), modified via novel 3.2 nm silica layer/silane-treated, (5) ZrO(2), modified via novel 5.8nm silica layer/silane-treated, and (6) ZrO(2), modified via novel 30.4 nm silica layer/silane-treated. Blocks were bonded to composite using Clearfil Esthetic cement. Blocks were stored in distilled water (37°C, 24h), then cut into microtensile bars (n=8/gp), then bond strengths were measured using a universal testing machine at 0, 1, 3, and 6 months. All groups were statistically analyzed (ANOVA, Tukey's, p<0.05). RESULTS: At 6 months (aging), all silica seed layer specimens displayed microtensile bond strength similar to CoJet specimens but less than that of silane-modified dental porcelain. CONCLUSION: The deposition of a silica layer on zirconia resulted in similar or superior long-term resin bond strength when compared to traditional silanation and bonding techniques for zirconia but lower than that for silane-treated dental porcelain.

Does the addition of glutamine to enteral feeds affect patient mortality?

OBJECTIVE: Studies have failed to consistently demonstrate improved survival in intensive care unit (ICU) patients receiving immune-modulating nutrient-enhanced enteral feeds when compared with standard enteral feeds. The objective was to study in a prospective fashion the effects of adding glutamine to standard or immune-modulated (supplemented with omega-3 fatty acids, beta-carotene, and amino acids such as glutamine and arginine) tube feeds. DESIGN: Prospective, unblinded study using sequential allocation. SETTING: A university surgical trauma ICU. PATIENTS: All surgical and trauma patients admitted to the surgical trauma ICU at a university hospital over a 3-yr period who were to receive enteral feeds (n = 185). INTERVENTIONS: Sequential assignment to three isocaloric, isonitrogenous diets was performed as follows: standard 1-kcal/mL feeds with added protein (group 1), standard feeds with the addition of 20-40 g/day (0.6 g/kg/day) glutamine (group 2), or an immune-modulated formula with similar addition of glutamine (group 3). The goal for all patients was 25-30 kcal/kg/day and 2 g/kg/day protein. MEASUREMENTS AND MAIN RESULTS: Patients were followed until discharge from the hospital. The primary end point was in-hospital mortality, and multiple secondary end points were recorded. In-hospital mortality for group 1 was 6.3% (four of 64) vs. 16.9% (ten of 59, p = .09) for group 2 and 16.1% (ten of 62, p = .09) for group 3. After controlling for age and severity of illness, the difference in mortality between patients receiving standard tube feeds and all patients receiving glutamine was not significant (p < or = .11). There were no statistically significant differences between the groups for secondary end points. CONCLUSIONS: The addition of glutamine to standard enteral feeds or to an immunomodulatory formula did not improve outcomes. These findings suggest that enteral glutamine should not be routinely administered to patients with surgical critical illness.

Biochemical and clinical aspects of the human flavin-containing monooxygenase form 3 (FMO3) related to trimethylaminuria.

Trimethylaminuria is a rare metabolic disorder that is associated with abnormal amounts of the dietary-derived trimethylamine. Excess unmetabolized trimethylamine in the urine, sweat and other body secretions confers a strong, foul body odor that can affect the individual's ability to work or engage in social activities. This review summarizes the biochemical aspects of the condition and the classification of the disorder into: 1) primary genetic form, 2) acquired form, 3) childhood forms, 4) transient form associated with menstruation, 5) precursor overload and 6) disease states. The genetic variability of the flavin-containing monooxygenase (form 3) that is responsible for detoxication and deodoration of trimethylamine is discussed and put in context with other variant forms of the flavin-containing monooxygenase (forms 1-5). The temporal-selective expression of flavin-containing monooxygenase forms 1 and 3 is discussed in terms of an explanation for childhood trimethylaminuria. Information as to whether variants of the flavin-containing monooxygenase form 3 contributes to hypertension and/or other diseases are presented. Discussion is provided outlining recent bioanalytical approaches to quantify urinary trimethylamine and trimethylamine N-oxide and plasma choline as well as data on self-reporting individuals tested for trimethylaminuria. Finally, trimethylaminuria treatment strategies and nutritional support are described including dietary sources of trimethylamine, vitamin supplementation and drug treatment and issues related to trimethylaminuria in pregnancy and lactation are discussed. The remarkable progress in the biochemical, genetic, clinical basis for understanding the trimethylaminuria condition is summarized and points to needs in the treatment of individuals suffering from trimethylaminuria.