Urine alkalization facilitates uric acid excretion

<p>Abstract</p> <p>Background</p> <p>Increase in the incidence of hyperuricemia associated with gout as well as hypertension, renal diseases and cardiovascular diseases has been a public health concern. We examined the possibility of facilitated excretion of uric acid by change in urine pH by managing food materials.</p> <p>Methods</p> <p>Within the framework of the Japanese government's health promotion program, we made recipes which consist of protein-rich and less vegetable-fruit food materials for H⁺-load (acid diet) and others composed of less protein but vegetable-fruit rich food materials (alkali diet). Healthy female students were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid and all cations (Na⁺,K⁺,Ca²⁺,Mg²⁺,NH₄⁺) and anions (Cl^-,SO₄^2-,PO₄^-) necessary for the estimation of acid-base balance were measured.</p> <p>Results</p> <p>Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO₄^2-] +organic acid-gut alkai) were linearly related with those of the excretion of acid (titratable acidity+ [NH₄⁺] - [HCO₃^-]), indicating that H⁺in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, where uric acid excretion increased from 302 mg/day at pH 5.9 to 413 mg/day at pH 6.5, despite the fact that the alkali diet contained a smaller purine load than the acid diet.</p> <p>Conclusion</p> <p>We conclude that alkalization of urine by eating nutritionally well-designed food is effective for removing uric acid from the body.</p

グラヤノトキシンD環の化学修飾

Grayanotoxin (GTX), one of the lipid-soluble Na+ channel openers, contains four rings (A, B, C and D) and the chemical groups essential for the pharmacological action are located on the A- and B-rings. To study the biological significance of functional groups on the D-ring, 51 new derivatives were prepared from α-dihydro GTX- 11 . These new compounds and the previously prepared GTXS ere directly applied to the intracellular phase of internally perfused squid giant axons

Differential Effects of Lipid-soluble Toxins on Sodium Channels and L-type Calcium Channels in Frog Ventricular Cells

The effect of grayanotoxin I (GTX I), veratridine and aconitine with either an external or internal concentration of 100 μM on L-type calcium (Ca) channels was studied using the whole cell patch clamp and internal dialysis methods. The experimental conditions for the modification of sodium (Na) channels induced by the internal application of these toxins was determined by showing sustained inward currents with depolarizing repetitive pulses. These toxins failed to generate any change in Ca channels under the same experimental protocol as for Na channels. However, external application of these toxins caused a moderate block of the Ca channels without changing the kinetics

Distinct sites regulating grayanotoxin binding and unbinding to D4S6 of Nav1.4 sodium channel as revealed by improved estimation of toxin sensitivity

Grayanotoxin (GTX) exerts selective effects on voltage-dependent sodium channels by eliminating fast sodium inactivation and causing a hyperpolarizing shift in voltagedependency of channel activation. In this study, we adopted a newly developed protocol that provides independent estimates of the binding and unbinding rate constants of GTX (kon and koff) to GTX-sites on the sodium channel protein, important in the molecular analysis of channel modification. Novel GTX-sites were determined in D2S6 (N784) and D3S6 (S1276) by means of site-directed mutagenesis; the results suggested that the GTX receptor consists of the S6 transmembrane segments of four quasi-homologous domains facing the ionconducting pore. We systematically introduced at two sites in D4S6 (Nav1.4-F1579 and Nav1.4-Y1586) amino acid substituents with residues containing hydrophobic, aromatic, charged, or polar groups. Generally, substitutions at F1579 increased both kon and koff, resulting in no prominent change in dissociation constant (Kd). It seems that the smaller the molecular size of the residue at Nav1.4-F1579, the larger the rates of kon and koff, indicating that this site acts as a gate regulating access of toxin molecules to a receptor site. Substitutions at Y1586 selectively increased koff but had virtually no effect on kon, thus causing a drastic increase in Kd. At position Y1586, a hydrophobic or aromatic amino acid side chain was required to maintain normal sensitivity to GTX. These results suggest that the residue at position Y1586 has a more critical role in mediating GTX binding than the one at position F1579. Here, we propose that the affinity of GTX to Nav1.4 sodium channels might be regulated by two residues (Phe and Tyr) at positions F1579 and Y1586, which respectively control access and binding of GTX to its receptor

Characterization of the Inactivation Process of the Sodium Channel in Frog Ventricular Cells

The voltage clamp experiments were conducted on single frog ventricular cells with the oil gap method for characterization of the sodium current (INa). The results obtained can be summarized as follows: 1. The falling phase of INa could be fitted by a single-exponential function when the series resistance was small (0.81-2.25 MO) and compensated. 2. Normalized steady-state inactivation (h∞) curve could be fitted by the equation h∞ = 1/(1 + exp(V-Vh)/k), where the half-inactivation voltage (Vh) was -59.8 mV and the slope factor (k) was 5.64 m V. No shift of this curve was observed throughout the experiment. 3. There was a delay of onset of inactivation development. 4. The time course for recovery of INa from inactivation exhibited a single time constant. 5. Almost all properties of the inactivation process of Na channel can be described by the original Hodgkin-Huxley's (H-H) kinetic model, except the presence of the delayed onset of inactivation. In order to incorporate this discrepancy, modification of H-H model is required, that the transition rate constant from the open state to the inactivated state may well be larger than that from the closed state to the inactivated state.This work was supported in part by a grant-in-aid from the Ministry of Education, Science and Culture of Japan (to I. S) and Tsuchiya Foundation (to M. Y)