22 research outputs found
Mizoribine provides effective treatment of sequential histological change of arteritis and reduction of inflammatory cytokines and chemokines in an animal model of Kawasaki disease
<p>Abstract</p> <p>Background</p> <p>Intravenous immunoglobulin (IVIg) treatment results in an effective response from patients with acute-phase Kawasaki disease (KD), but 16.5% of them remain nonresponsive to IVIg. To address this therapeutic challenge, we tried a new therapeutic drug, mizoribine (MZR), in a mouse model of KD, which we have established using injections of <it>Candida albicans </it>water-soluble fractions (CAWS).</p> <p>Methods</p> <p>CAWS (4 mg/mouse) were injected intraperitoneally into C57BL/6N mice for 5 consecutive days. MZR or IgG was administered for 5 days. After 4 weeks, the mice were sacrificed and autopsied, the hearts were fixed in 10% neutral formalin, and plasma was taken to measure cytokines and chemokines using the Bio-Plex system.</p> <p>The incidence of panvasculitis in the coronary arteries and aortic root was 100% in the control group. The incidence of panvasculitis in the MZR group decreased to 50%. Moreover, the scope and severity of the inflammation of those sites were significantly reduced in the MZR group as well as the IgG group. On the other hand, increased cytokines and chemokines, such as IL-1α, TNF-α, KC, MIP-1α, GM-CSF, and IL-13, in the nontreatment group were significantly suppressed by treatment with MZR, but the MCP-1 level increased. In addition, IL-1α, TNF-α, IL-10, IL-13, and MIP-1α were suppressed by treatment in the IgG group.</p> <p>Results</p> <p>The incidence of panvasculitis in the coronary arteries and aortic root was 100% in the control group. The incidence of panvasculitis in the MZR group decreased to 50%. Moreover, the scope and severity of the inflammation of those sites were significantly reduced in the MZR group as well as the IgG group. On the other hand, increased cytokines and chemokines, such as IL-1α TNF-α, KC, MIP-1α, GM-CSF, and IL-13, in the nontreatment group were significantly suppressed by treatment with MZR, but the MCP-1 level increased. In addition, IL-1α, TNF-α, IL-10, IL-13, and MIP-1α were suppressed by treatment in the IgG group.</p> <p>Conclusion</p> <p>MZR treatment suppressed not only the incidence, range, and degree of vasculitis, but also inflammatory cytokines and chemokines in the plasma of the KD vasculitis model mice, suggesting that MZR may be useful for treatment of KD.</p
Prevention of hypoglycemia by intermittent-scanning continuous glucose monitoring device combined with structured education in patients with type 1 diabetes mellitus : A randomized, crossover trial
Aims: We conducted a randomized, crossover trial to compare intermittent-scanning continuous glucose monitoring (isCGM) device with structured education (Intervention) to self-monitoring of blood glucose (SMBG) (Control) in the reduction of time below range.
Methods: This crossover trial involved 104 adults with type 1 diabetes mellitus (T1DM) using multiple daily injections. Participants were randomly allocated to either sequence Intervention/Control or sequence Control/Intervention. During the Intervention period which lasted 84 days, participants used the first-generation FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) and received structured education on how to prevent hypoglycemia based on the trend arrow and by frequent sensor scanning (≥10 times a day). Confirmatory SMBG was conducted before dosing insulin. The Control period lasted 84 days. The primary endpoint was the decrease in the time below range (TBR; <70 mg/dL).
Results: The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index >5 was significantly reduced (8.6 % vs 23.7 %, P < 0.001).
Conclusions: The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM
Inversion of the Stereochemistry around the Sulfur Atom of the Axial Methionine Side Chain through Alteration of Amino Acid Side Chain Packing in Hydrogenobacter thermophilus Cytochrome <i>c</i><sub>552</sub> and Its Functional Consequences
In cytochrome <i>c</i>,
the coordination of the axial
Met S<sub>δ</sub> atom to the heme Fe atom occurs in one of
two distinctly different stereochemical manners, i.e., <i>R</i> and <i>S</i> configurations, depending upon which of the
two lone pairs of the S<sub>δ</sub> atom is involved in the
bond; hence, the Fe-coordinated S<sub>δ</sub> atom becomes a
chiral center. In this study, we demonstrated that an alteration of
amino acid side chain packing induced by the mutation of a single
amino acid residue, i.e., the A73V mutation, in Hydrogenobacter
thermophilus cytochrome <i>c</i><sub>552</sub> (HT) forces the inversion of the stereochemistry around the S<sub>δ</sub> atom from the <i>R</i> configuration [Travaglini-Allocatelli,
C., et al. (2005) <i>J. Biol. Chem</i>. <i>280</i>, 25729–25734] to the <i>S</i> configuration. Functional
comparison between the wild-type HT and the A73V mutant possessing
the <i>R</i> and <i>S</i> configurations as to
the stereochemistry around the S<sub>δ</sub> atom, respectively,
demonstrated that the redox potential (<i>E</i><sub>m</sub>) of the mutant at pH 6.00 and 25 °C exhibited a positive shift
of ∼20 mV relative to that of the wild-type HT, i.e., 245 mV,
in an entropic manner. Because these two proteins have similar enthalpically
stabilizing interactions, the difference in the entropic contribution
to the <i>E</i><sub>m</sub> value between them is likely
to be due to the effect of the conformational alteration of the axial
Met side chain associated with the inversion of the stereochemistry
around the S<sub>δ</sub> atom due to the effect of mutation
on the internal mobility of the loop bearing the axial Met. Thus,
the present study demonstrated that the internal mobility of the loop
bearing the axial Met, relevant to entropic control of the redox function
of the protein, is affected quite sensitively by the contextual stereochemical
packing of amino acid side chains in the proximity of the axial Met