Učinak dodataka prehrani acetaminofena i vitamina C na stres i upalni odgovor u korejske autohtone pasmine goveda cijepljene protiv slinavke i šapa - kratko priopćenje

This study evaluated the effect of a combination of acetaminophen and vitamin C (CAV) for reduction of stress and inflammatory responses in calves vaccinated with foot-and-mouth disease (FMD) vaccine. Twenty-five calves were divided into five groups of 5 calves. The negative control was non-vaccination and non-drug treatment. The positive control, and experimental groups I, II and III were vaccinated with FMD vaccine and treated with CAV at concentrations of 0.0, 0.5, 1.0 and 2.0 kg/ton feed, respectively, for five consecutive days post-vaccination. On day 5 post-treatment, serum cortisols and tumor necrosis factor-α (TNF-α) were significantly decreased in all treatment groups compared with the positive control (P<0.05). However, there was no significant difference in serum cortisol and TNF-α levels between experimental groups I and II and the negative control. The results from this study suggest that CAV may be a useful drug for control of the stress and inflammation caused by FMD vaccination in calves.U ovom se radu istražuje učinak kombinacije acetaminofena i vitamina C (CAV) na smanjenje stresa i upalnog odgovora u teladi cijepljene protiv slinavke i šapa. Ukupno 25 životinja podijeljeno je u pet skupina po pet životinja. Životinje u negativnoj kontrolnoj skupini nisu cijepljene i nisu dobile dodatke prehrani. Životinje u pozitivnoj kontrolnoj skupini i pokusnim skupinama I, II i III cijepljene su cjepivom protiv slinavke i šapa i dobile su dodatak prehrani CAV u koncentracijama od 0,0, 0,5, 1,0 i 2,0 kg/toni hrane, pet uzastopnih dana poslije cijepljenja. Peti dan nakon tretmana serumski kortizol i faktor nekroze tumora alfa (TNF-α) bili su znakovito smanjeni u svim pokusnim skupinama u usporedbi s pozitivnom kontrolnom skupinom (P<0,05). Nije bilo znakovite razlike u vrijednostima serumskog kortizola i TNF-α između pokusne skupine 1 i 2 i negativne kontrolne skupine. Rezultati ovoga istraživanja upućuju na to da bi CAV mogao biti koristan u kontroli stresa i upale uzrokovane cjepivom protiv slinavke i šapa u teladi

Mutant Insulin Degrading Enzyme and Methods of Use

In one aspect, the present invention provides an isolated mutant insulin degrading enzyme (IDE) having an amino acid sequence that is at least 90% identical to SEQ ID NO:1 over its entire length and comprises at least one amino acid substitution at any of amino acid residues 332, 339, 341, 359, 360, 361, 374, 429, 609, 898, 899 or 901 of the sequence. The mutant IDE has a differential activity relative to that of wild-type IDE. Also provided is a polynucleotide encoding the polypeptide of the invention

A Monomeric Variant of Insulin Degrading Enzyme (IDE) Loses Its Regulatory Properties

Background: Insulin degrading enzyme (IDE) is a key enzyme in the metabolism of both insulin and amyloid beta peptides. IDE is unique in that it is subject to allosteric activation which is hypothesized to occur through an oligomeric structuture. Methodology/Principal Findings: IDE is known to exist as an equilibrium mixture of monomers, dimers, and higher oligomers, with the dimer being the predominant form. Based on the crystal structure of IDE we deleted the putative dimer interface in the C-terminal region, which resulted in a monomeric variant. Monomeric IDE retained enzymatic activity, however instead of the allosteric behavior seen with wild type enzyme it displayed Michaelis-Menten kinetic behavior. With the substrate Abz-GGFLRKHGQ-EDDnp, monomeric IDE retained,25 % of the wild type activity. In contrast with the larger peptide substrates b-endorphin and amyloid b peptide 1–40, monomeric IDE retained only 1 to 0.25 % of wild type activity. Unlike wild type IDE neither bradykinin nor dynorphin B-9 activated the monomeric variant of the enzyme. Similarly, monomeric IDE was not activated by polyphosphates under conditions in which the activity of wild type enzyme was increased more than 50 fold. Conclusions/Significance: These findings serve to establish the dimer interface in IDE and demonstrate the requirement for an oligomeric form of the enzyme for its regulatory properties. The data support a mechanism where the binding of activators to oligomeric IDE induces a conformational change that cannot occur in the monomeric variant. Since

Evaluation of the transporter-mediated herb-drug interaction potential of DA-9801, a standardized dioscorea extract for diabetic neuropathy, in human in vitro and rat in vivo

BACKGROUND: Drug transporters play important roles in the absorption, distribution, and elimination of drugs and thereby, modulate drug efficacy and toxicity. With a growing use of poly pharmacy, concurrent administration of herbal extracts that modulate transporter activities with drugs can cause serious adverse reactions. Therefore, prediction and evaluation of drug-drug interaction potential is important in the clinic and in the drug development process. DA-9801, comprising a mixed extract of Dioscoreae rhizoma and Dioscorea nipponica Makino, is a new standardized extract currently being evaluated for diabetic peripheral neuropathy in a phase II clinical study. METHOD: The inhibitory effects of DA-9801 on the transport functions of organic cation transporter (OCT)1, OCT2, organic anion transporter (OAT)1, OAT3, organic anion transporting polypeptide (OATP)1B1, OATP1B3, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP) were investigated in HEK293 or LLC-PK1 cells. The effects of DA-9801 on the pharmacokinetics of relevant substrate drugs of these transporters were also examined in vivo in rats. RESULTS: DA-9801 inhibited the in vitro transport activities of OCT1, OCT2, OAT3, and OATP1B1, with IC(50) values of 106, 174, 48.1, and 273 μg/mL, respectively, while the other transporters were not inhibited by 300 μg/mL DA-9801. To investigate whether this inhibitory effect of DA-9801 on OCT1, OCT2, and OAT3 could change the pharmacokinetics of their substrates in vivo, we measured the pharmacokinetics of cimetidine, a substrate for OCT1, OCT2, and OAT3, and of furosemide, a substrate for OAT1 and OAT3, by co-administration of DA-9801 at a single oral dose of 1,000 mg/kg. Pre-dose of DA-9801 5 min or 2 h prior to cimetidine administration decreased the C(max) of cimetidine in rats. However, DA-9801 did not affect the elimination parameters such as half-life, clearance, or amount excreted in the urine, suggesting that it did not inhibit elimination process of cimetidine, which is governed by OCT1, OCT2, and OAT3. Moreover, DA-9801 did not affect the pharmacokinetic characteristics of furosemide, as evidenced by its unchanged pharmacokinetic parameters. CONCLUSION: Inhibitory effects of DA-9801 on OCT1, OCT2, and OAT3 observed in vitro may not necessarily translate into in vivo herb-drug interactions in rats even at its maximum effective dose

Cysteine 904 is required for maximal insulin degrading enzyme activity and polyanion activation

Cysteine residues in insulin degrading enzyme have been reported as non-critical for its activity. We found that converting the twelve cysteine residues in rat insulin degrading enzyme (IDE) to serines resulted in a cysteine-free form of the enzyme with reduced activity and decreased activation by polyanions. Mutation of each cysteine residue individually revealed cysteine 904 as the key residue required for maximal activity and polyanion activation, although other cysteines affect polyanion binding to a lesser extent. Based on the structure of IDE, Asn 575 was identified as a potential hydrogen bond partner for Cys904 and mutation of this residue also reduced activity and decreased polyanion activation. The oligomerization state of IDE did not correlate with its activity, with the dimer being the predominant form in all the samples examined. These data suggest that there are several conformational states of the dimer that affect activity and polyanion activation

The Quality of Reporting of Intervention Studies in the Korean Journal of Women Health Nursing (KJWHN): Based on the TREND Guidelines

PURPOSE: This study was done to evaluate quality of reports of non-randomized controlled quasi-experimental study articles published in the Korean Journal of Women Health Nursing (KJWHN). METHODS: A search was done for experimental studies assessing intervention effects among all articles published in the KJWHNfrom 2008 to 2013. Original articles were reviewed and analyzed according to the 22 checklist items of the guidelines for Transparent Reporting for Evaluations with Non-randomized Designs (TREND). RESULTS: Thirty-five articles on experimental studies were identified. The evaluation of the quality of reporting in these experimental studies found that there was a wide variety in the level of satisfying the TREND checklist. In particular, according to TREND topics, low levels of reporting quality were found for &quot;title &amp; abstract (only for information on how units were allocated to the intervention)&quot;, &quot;outcomes in methods&quot;, &quot;assignment in methods&quot;, &quot;blinding in methods&quot;, &quot;recruitment in results&quot;, &quot;baseline data in results&quot;, &quot;interpretation in discussion (especially intervention mechanism and success or barriers), &quot;generalizability in discussion&quot;. CONCLUSION: Results indicate that adherence to TREND guidelines varied in experimental studies published in the KJWHN suggesting the recommendation that for higher levels of complete reporting, TREND guidelines be used in reports on experimental studies

Research Trend of Women's Health in Korean Nursing Journals (2010~2015)

PURPOSE: To explore trends of women&apos;s health in nursing research by analyzing articles on women aged 13 years or older that were published in Korean Journal for Women Health Nursing from 2010 to 2015. METHODS: Seven focus areas were identified and modified to reflect integrative conceptual models of women&apos;s health: maternity care, menstrual concerns, health problems in women, gender influences on health risks, social influences on women&apos;s health, women and health care policy, and sexual health and violence against women. A total of 383 studies were analyzed according to these seven focus areas. RESULTS: Health problems in women, maternity care, and societal influences on women&apos;s health were the most widely studied topics in Korean women&apos;s health. There was increased attention to societal influences on women&apos;s health and gender influences on health risk. However, these areas are still limited in nursing research. Only 1% of these studies were in area of women&apos;s health policy. CONCLUSION: More studies in area of sexual health and violence against women are needed. Studies in area of women and health care policy are also needed to improve women&apos;s health in Korea

Prehospital Delay, Precipitants of Admission, and Length of Stay in Patients With Exacerbation of Heart Failure

BACKGROUND: Factors that precipitate hospitalization for exacerbation of heart failure provide targets for intervention to prevent hospitalizations. OBJECTIVES: To describe demographic, clinical, behavioral, and psychosocial factors that precipitate admission for exacerbation of heart failure and assess the relationships between precipitating factors and delay before hospitalization, and between delay time and length of hospital stay. METHODS: All admissions in 12 full months to a tertiary medical center were reviewed if the patient had a discharge code related to heart failure. Data on confirmed admissions for exacerbation of heart failure were included in the study. Electronic and paper medical records were reviewed to identify how long it took patients to seek care after they became aware of signs and symptoms, factors that precipitated exacerbation, and discharge details. RESULTS: Exacerbation of heart failure was confirmed in 482 patients. Dyspnea was the most common symptom (92.5% of patients), and 20.3% of patients waited until they were severely dyspneic before seeking treatment. The most common precipitating factor was poor medication adherence. Delay times from symptom awareness to seeking treatment were shorter in patients who had a recent change in medicine for heart failure, renal failure, or poor medication adherence and longer in patients with depressive symptoms and hypertension. CONCLUSIONS: Depressive symptoms, recent change in heart failure medicine, renal failure, poor medication adherence, and hypertension are risk factors for hospitalizations for exacerbation of heart failure