Biomedical subjects

Shinya Ito

Publications and source records attributed to Shinya Ito.

43 records · Page 3Linked to original sources

PubMed2003

The safety of St. John's wort (Hypericum perforatum) during breastfeeding.

BACKGROUND: We examined the safety of St. John's wort to nursing mothers and their infants. METHOD: A prospective, observational, cohort study was conducted. Thirty-three breastfeeding women receiving St. John's wort (Group 1) who contacted our teratogen/toxicant counseling service regarding the safety of St. John's wort during breastfeeding were followed up between May 1999 and April 2001. These women were compared with 101 disease-matched (Group 2) and 33 age- and parity-matched nondisease controls (Group 3). Information collected included maternal and neonatal demographics, breastfeeding duration, use of St. John's wort, maternal and infant adverse events, infant weight over the first year of life, and whether or not the mother experienced a decrease in lactation. RESULTS: There were no statistically significant differences found in maternal or infant demographics or maternal adverse events. Whereas only 1 infant each in Groups 2 and 3 was reported to be colicky, there were 2 cases of "colic," 2 of "drowsiness," and 1 of "lethargy" in Group 1 (p <.01; Group 1 vs. Group 2, p <.01; Group 1 vs. Group 3, p =.20). Although 3 of these women in Group 1 consulted their doctor, specific medical treatment was not required. No significant difference was observed in the frequency of maternal report of decreased milk production among the groups, nor was a difference found in infant weight over the first year of life. CONCLUSION: These results provide a framework for the management of breastfeeding women receiving St. John's wort.

Antidepressive Agents↗

PubMed2003

The kidney--the body's playground for drugs: an overview of renal drug handling with selected clinical correlates.

A greater understanding of transport mechanisms contributing to renal drug handling may be useful in predicting drug clearance and drug interactions. Renal clearance is a dynamic process expressed as the sum of the rates of glomerular filtration and tubular secretion minus the rate of tubular reabsorption. Because the transport of drugs is often against a concentration gradient, renal secretion is mostly an active process involving a variety of transporter mechanisms. Discoveries from molecular biology techniques and gene 'knock-out' experiments have identified a variety of renal tubular proteins responsible for the transport of organic cations, organic anions, neutral and cationic hydrophobic compounds, anionic conjugates and specific agents such as prostaglandins. The discovery of a P-glycoprotein (P-gp) transporter at the apical membrane of renal tubular cells is particularly important. By elucidating compounds that act as substrates, inhibitors or inducers of transport proteins, pharmacologists and clinicians may better understand renal drug clearance. This paper provides a brief overview of several identified renal transport proteins including organic anion transporters, organic cation transporters, ATP-dependent transporters (multidrug resistance [P-gp] and multi-drug resistance associated protein), nucleoside transporters (sodium-dependent purine nucleoside transporter and concentrative nucleoside transporter 1) and peptide transporters. A special focus on known P-gp-mediated drug interactions is included to demonstrate the clinical relevance of transporter protein science. At the patient level, this may lead to novel approaches to alter in vivo pharmacokinetics and improve drug safety through a greater understanding of toxic substrate clearance and drug interactions.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Use of lipid-lowering agents (statins) during pregnancy.

QUESTION: A 34-year-old patient of mine is taking a 'statin' for hyperlipidemia. She is planning pregnancy and is worried about the safety of the drug. How should I advise her? ANSWER: Limited evidence from animal and human studies indicates that statins should not be taken during pregnancy. If a patient is inadvertently exposed during pregnancy, however, termination does not appear to be medically indicated.

Adult↗

PubMed2003

From bench to bedside: utilization of an in vitro model to predict potential drug-drug interactions in the kidney: the digoxin-mifepristone example.

Drug interactions are a common source of drug-induced toxicity. For drugs with narrow therapeutic windows, such as digoxin, an understanding of the potential mechanisms by which drugs might interact is essential to clinical practice. This article describes the utility of a renal tubular cell culture model in the prediction of drug interactions involving P-glycoprotein. Digoxin is a cardiac glycoside that undergoes active secretion in the renal tubules by the MDR1 (P-glycoprotein) drug efflux pump. Mifepristone (RU486) is a recently introduced abortifacient that is largely unstudied in terms of drug-drug interactions. The authors used an in vitro model to study the effects of mifepristone on the renal tubular secretion and cellular uptake of digoxin by Madin-Darby canine kidney (MDCK) cells. Mifepristone significantly inhibited the renal tubular secretion of digoxin (p = 0.0005), without interfering with its ability to enter the renal tubular cell. Similar results were found with the P-glycoprotein substrate vinblastine. The findings suggest that drug interactions may result if mifepristone is administered with P-glycoprotein substrates, highlighting the usefulness of this model in the study of not only common but also rare combinations of drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

Matrix effect and correction by standard addition in quantitative liquid chromatographic-mass spectrometric analysis of diarrhetic shellfish poisoning toxins.

An evaluation of the feasibility of liquid chromatography-mass spectrometry (LC-MS) with atmospheric pressure ionization was made for quantitation of four diarrhetic shellfish poisoning toxins, okadaic acid, dinophysistoxin-1, pectenotoxin-6 and yessotoxin in scallops. When LC-MS was applied to the analysis of scallop extracts, large signal suppressions were observed due to coeluting substances from the column. To compensate for these matrix signal suppressions, the standard addition method was applied. First, the sample was analyzed and then the sample involving the addition of calibration standards is analyzed. Although this method requires two LC-MS runs per analysis, effective correction of quantitative errors was found.

Animals↗

PubMed2002

Perinatal outcome following third trimester exposure to paroxetine.

BACKGROUND: Paroxetine hydrochloride is commonly used for maternal depression, panic disorder, and obsessive-compulsive disorder. The drug readily crosses the human placenta. Although it does not appear to increase teratogenic risk, there have been case reports of neonatal withdrawal. Symptoms were described soon after birth and lasted up to 1 month. OBJECTIVE: To investigate whether there is a clinically important discontinuation syndrome in neonates exposed to paroxetine in utero. METHODS: Prospective, controlled cohort study. PATIENTS: Fifty-five pregnant women counseled prospectively by the Motherisk program in Toronto, Ontario, regarding third-trimester exposure to paroxetine and their infants were included in the study group. Pregnant women who discontinued paroxetine before the third trimester or those receiving other drugs known to cause withdrawal-type symptoms, such as opioids or benzodiazepines, were excluded. A comparison group of 27 women using paroxetine during the first or second trimester and 27 women using nonteratogenic drugs were matched for maternal age, gravity, parity, social drug use, and nonteratogenic drug use. RESULTS: Of the 55 neonates exposed to paroxetine in late gestation, 12 had complications necessitating intensive treatment and prolonged hospitalization. The most prevalent clinical picture was respiratory distress (n = 9), followed by hypoglycemia (n = 2), and jaundice (n = 1). The symptoms disappeared within 1 to 2 weeks. In the comparison group, only 3 infants experienced complications (P =.03). In logistic regression, only third-trimester exposure to paroxetine was associated with neonatal distress (odds ratio, 9.53; 95% confidence interval, 1.14-79.3). CONCLUSION: When used near term, paroxetine is associated with a high rate of neonatal complications, possibly caused by its common discontinuation syndrome.

Adult↗

PubMed2002

Enhanced mass detection of oligonucleotides using reverse-phase high-performance liquid chromatography/electrospray ionization ion-trap mass spectrometry.

A new method providing enhanced sensitivity for the analysis of oligonucleotides using an on-line coupled system of reversed-phase high-performance liquid chromatography (RP-HPLC) and electrospray ionization ion-trap mass spectrometry (ESI-MS) has been developed. The presented method allows the use of the standard gradient elution of 0.1 M triethylammonium acetate (TEAA) buffer (adjusted to pH 7.0 with acetic acid) and acetonitrile that is typically used for the separation of oligonucleotides in RP-HPLC. An added feature of this method is the ability to combine and mix additional 0.1 M imidazole in acetonitrile after the separation column for improved ESI-MS performance. This is similar to the post-column reaction method in liquid chromatography (LC) and the liquid sheath flow method in LC/ESI-MS, both of which offer the advantage of not compromising the chromatographic separation conditions. The application of this new method is demonstrated to afford improved sensitivity for the analysis of oligonucleotides (20-50 mer) via on-line coupled HPLC/ESI-MS analysis and purification systems.

Chromatography, High Pressure Liquid↗