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Find video protocols related to scientific articles indexed in Pubmed.
H1-antihistamines exacerbate high-fat diet-induced hepatic steatosis in wild-type but not in apolipoprotein E knockout mice.
Am. J. Physiol. Gastrointest. Liver Physiol.
PUBLISHED: 05-22-2014
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We examined the effects of two over-the-counter H1-antihistamines on the progression of fatty liver disease in male C57Bl/6 wild-type and apolipoprotein E (ApoE)-/- mice. Mice were fed a high-fat diet (HFD) for 3 mo, together with administration of either cetirizine (4 mg/kg body wt) or fexofenadine (40 mg/kg body wt) in drinking water. Antihistamine treatments increased body weight gain, gonadal fat deposition, liver weight, and hepatic steatosis in wild-type mice but not in ApoE-/- mice. Lobular inflammation, acute inflammation, and necrosis were not affected by H1-antihistamines in either genotype. Serum biomarkers of liver injury tended to increase in antihistamine-treated wild-type mice. Serum level of glucose was increased by fexofenadine, whereas lipase was increased by cetirizine. H1-antihistamines reduced the mRNA expression of ApoE and carbohydrate response element-binding protein in wild-type mice, without altering the mRNA expression of sterol regulatory element-binding protein 1c, fatty acid synthase, or ApoB100, in either genotype. Fexofenadine increased both triglycerides and cholesterol ester, whereas cetirizine increased only cholesterol ester in liver, with a concomitant decrease in serum triglycerides by both antihistamines in wild-type mice. Antihistamines increased hepatic levels of conjugated bile acids in wild-type mice, with the effect being significant in fexofenadine-treated animals. The increase was associated with changes in the expression of organic anion transport polypeptide 1b2 and bile salt export pump. These results suggest that H1-antihistamines increase the progression of fatty liver disease in wild-type mice, and there seems to be an association between the severity of disease, presence of ApoE, and increase in hepatic bile acid levels.
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Health risks caused by short term exposure to ultrafine particles generated by residential wood combustion: a case study of Temuco, Chile.
Environ Int
PUBLISHED: 01-07-2014
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Temuco is one of the most highly wood smoke polluted cities in Chile; however, there is scarce evidence of respiratory morbidity due to fine particulate matter. We aimed to estimate the relationship between daily concentration of ultrafine particles (UFP), with an aerodynamic diameter ? 0.1 ?m, and outpatient visits for respiratory illness at medical care centers of Temuco, Chile, from August the 20th, 2009 to June the 30th, 2011. The Air Pollution Health Effects European Approach (APHEA2) protocol was followed, and a multivariate semi-parametric Poisson regression model was fitted with GAM techniques using R-Project statistical package; controlling for trend, seasonality, and confounders. The daily UFP were measured by a MOUDI NR-110 sampler. We found that results of the statistical analyses show significant associations between UFP and respiratory outpatient visits, with the elderly (population ? 65 years), being the group that presented the greatest risk. An interquartile increase of 4.73 ?g/m(3) in UFP (lag 5 days) was associated with respiratory outpatient visits with a relative risk (RR) of 1.1458 [95% CI (1.0497-1.2507)] for the elderly. These results show novel findings regarding the relevance of daily UFP concentrations and health risk, especially for susceptible population in a wood smoke polluted city.
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Chronic ingestion of H1-antihistamines increase progression of atherosclerosis in apolipoprotein E-/- mice.
PLoS ONE
PUBLISHED: 01-01-2014
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Although increased serum histamine levels and H1R expression in the plaque are seen in atherosclerosis, it is not known whether H1R activation is a causative factor in the development of the disease, or is a host defense response to atherogenic signals. In order to elucidate how pharmacological inhibition of histamine receptor 1 (H1R) signaling affects atherogenesis, we administered either cetirizine (1 and 4 mg/kg. b.w) or fexofenadine (10 and 40 mg/kg. b.w) to ApoE-/- mice maintained on a high fat diet for three months. Mice ingesting a low dose of cetirizine or fexofenadine had significantly higher plaque coverage in the aorta and cross-sectional lesion area at the aortic root. Surprisingly, the higher doses of cetirizine or fexofenadine did not enhance atherosclerotic lesion coverage over the controls. The low dose of fexofenadine, but not cetirizine, increased serum LDL cholesterol. Interestingly, the expression of iNOS and eNOS mRNA was increased in aortas of mice on high doses of cetirizine or fexofenadine. This may be a compensatory nitric oxide (NO)-mediated vasodilatory mechanism that accounts for the lack of increase in the progression of atherosclerosis. Although the administration of cetirizine did not alter blood pressure between the groups, there was a positive correlation between blood pressure and lesion/media ratio at the aortic root in mice receiving the low dose of cetirizine. However, this association was not observed in mice treated with the high dose of cetirizine or either doses of fexofenadine. The macrophages or T lymphocytes densities were not altered by low doses of H1-antihistamines, whereas, high doses decreased the number of macrophages but not T lymphocytes. The number of mast cells was decreased only in mice treated with low dose of fexofenadine. These results demonstrate that chronic ingestion of low therapeutic doses of cetirizine or fexofenadine enhance progression of atherosclerosis.
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Quantification of the transporter substrate fexofenadine in cell lysates by liquid chromatography/tandem mass spectrometry.
Rapid Commun. Mass Spectrom.
PUBLISHED: 07-19-2011
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Drug-drug interactions at transporters present a significant and under-investigated clinical problem. Investigations of specific transporter functions and screening for potential drug-drug interactions, both in vitro and especially in vivo, will require validated experimental probes. Fexofenadine, an approved, well-tolerated drug, is a promising probe for studies of membrane transporter function. Although fexofenadine pharmacokinetics are known to be controlled by transporters, the contributions of individual transporters have not been defined. We have developed a rapid, specific, and sensitive analytical method for quantitation of fexofenadine to support this work. This liquid chromatography/tandem mass spectrometry (LC/MS/MS) method quantifies fexofenadine in cell lysates from in vitro studies using cetirizine as the internal standard. Cell lysates were prepared for analysis by acetonitrile precipitation. Analytes were then separated by gradient reversed-phase chromatography and analyzed by tandem mass spectrometry using the m/z 502.17/466.2 transition for fexofenadine and m/z 389.02/201.1 for cetirizine. The method exhibited a linear dynamic range of 1-500 ng/mL for fexofenadine in cell lysates. The lower limit of quantification was 1 ng/mL with a relative standard deviation of less than 5%. Intra- and inter-day precision and accuracy were within the limits presented in the FDA guidelines for bioanalysis. We also will validate this method to support not only the quantification of fexofenadine, but also other probe drugs for drug-drug interaction studies. This method for quantification will facilitate the use of fexofenadine as a probe drug for characterization of transporter activity.
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Buspirone, fexofenadine, and omeprazole: quantification of probe drugs and their metabolites in human plasma.
J Pharm Biomed Anal
PUBLISHED: 03-25-2011
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Probe drugs are critical tools for the measurement of drug metabolism and transport activities in human subjects. Often several probe drugs are administered simultaneously in a "cocktail". This cocktail approach requires efficient analytical methods for the simultaneous quantitation of multiple analytes. We have developed and validated a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of three probe drugs and their metabolites in human plasma. The analytes include omeprazole and its metabolites omeprazole sulfone and 5-hydroxyomeprazole; buspirone and its metabolite 1-[2-pyrimidyl]-piperazine (1PP); and fexofenadine. These analytes and the internal standard lansoprazole were extracted from plasma using protein precipitation with acetonitrile. Gradient reverse-phase chromatography was performed with 7.5mM ammonium bicarbonate and acetonitrile, and the analytes were quantified in positive ion electrospray mode with multiple reaction monitoring. The method was validated to quantify the concentration ranges of 1.0-1000ng/ml for omeprazole, omeprazole sulfone, 5-hydroxyomeprazole, and fexofenadine; 0.1-100ng/ml for buspirone, and 1.0-100ng/ml for 1PP. These linear ranges span the plasma concentrations for all of the analytes from probe drug studies. The intra-day precision was between 2.1 and 16.1%, and the accuracy ranged from 86 to 115% for all analytes. Inter-day precision and accuracy ranged from 0.3 to 14% and from 90 to 110%, respectively. The lower limits of quantification were 0.1ng/ml for buspirone and 1ng/ml for all other analytes. This method provides a fast, sensitive, and selective analytical tool for quantification of the six analytes in plasma necessary to support the use of this probe drug cocktail in clinical studies.
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Dopamine receptor alterations in female rats with diet-induced decreased brain docosahexaenoic acid (DHA): interactions with reproductive status.
Nutr Neurosci
PUBLISHED: 07-31-2010
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Decreased tissue levels of n-3 (omega-3) fatty acids, particularly docosahexaenoic acid (DHA), are implicated in the etiologies of non-puerperal and postpartum depression. This study examined the effects of a diet-induced loss of brain DHA content and concurrent reproductive status on dopaminergic parameters in adult female Long-Evans rats. An alpha-linolenic acid-deficient diet and breeding protocols were used to produce virgin and parous female rats with cortical phospholipid DHA levels 20-22% lower than those fed a control diet containing adequate alpha-linolenic acid. Decreased brain DHA produced a significant main effect of decreased density of ventral striatal D(2)-like receptors. Virgin females with decreased DHA also exhibited higher density of D(1)-like receptors in the caudate nucleus than virgin females with normal DHA. These receptor alterations are similar to those found in several rodent models of depression, and are consistent with the proposed hypodopaminergic basis for anhedonia and motivational deficits in depression.
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Design, recruitment, and retention of African-American smokers in a pharmacokinetic study.
BMC Med Res Methodol
PUBLISHED: 01-19-2010
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African-Americans remain underrepresented in clinical research despite experiencing a higher burden of disease compared to all other ethnic groups in the United States. The purpose of this article is to describe the study design and discuss strategies used to recruit and retain African-American smokers in a pharmacokinetic study.
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Using descriptive assessment in the treatment of bite acceptance and food refusal.
Behav Modif
PUBLISHED: 08-12-2009
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The feeding behaviors of two children who maintained failure to thrive diagnoses and displayed food refusal are assessed in their homes. Descriptive assessments are used to identify schedules of consequence provided by each childs care providers for bite acceptance and food refusal behaviors. Assessments reveal rich schedules of praise and access to social interaction and preferred activities for bite acceptance and escape for food refusal. These schedule arrangements result in hypotheses that modifications to the schedule of praise and access to social interaction and preferred activities for bite acceptance would result in little to no effect and that modifications to the schedule of escape for food refusal would be necessary for treatment success. Successful interventions are subsequently implemented by manipulating the existing schedules of escape for food refusal by each childs care providers. Implications for the use of descriptive assessments for feeding problems are discussed.
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Functional analysis and treatment of multiply controlled inappropriate mealtime behavior.
J Appl Behav Anal
PUBLISHED: 02-01-2009
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Functional analyses identified children whose inappropriate mealtime behavior was maintained by escape and adult attention. Function-based extinction procedures were tested individually and in combination. Attention extinction alone did not result in decreases in inappropriate mealtime behavior or a significant increase in acceptance. By contrast, escape extinction alone resulted in a decrease in inappropriate mealtime behavior and an increase in acceptance. However, inappropriate mealtime behavior did not decrease to clinically acceptable levels. A combined extinction technique (i.e., escape and attention extinction) resulted in a decrease in inappropriate mealtime behavior to clinically acceptable levels and high and stable acceptance.
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Effects of menthol on the pharmacokinetics of bupropion among Black smokers.
Nicotine Tob. Res.
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Despite the widespread use of mentholated cigarettes, lower cessation rates, and disproportionately high smoking-related morbidity among Blacks, the possible role of menthol in smokers response to pharmacotherapy has not been well-studied. This study examined the effects of menthol on the pharmacokinetic (PK) profiles of bupropion and its principal metabolites, hydroxybupropion, threohydrobupropion, and erythrohydrobupropion among Black smokers.
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Oral ciclopirox olamine displays biological activity in a phase I study in patients with advanced hematologic malignancies.
Am. J. Hematol.
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The antimycotic ciclopirox olamine is an intracellular iron chelator that has anticancer activity in vitro and in vivo. We developed an oral formulation of ciclopirox olamine and conducted the first-in-human phase I study of this drug in patients with relapsed or refractory hematologic malignancies (Trial registration ID: NCT00990587). Patients were treated with 5-80 mg/m(2) oral ciclopirox olamine once daily for five days in 21-day treatment cycles. Pharmacokinetic and pharmacodynamic companion studies were performed in a subset of patients. Following definition of the half-life of ciclopirox olamine, an additional cohort was enrolled and treated with 80 mg/m(2) ciclopirox olamine four times daily. Adverse events and clinical response were monitored throughout the trial. Twenty-three patients received study treatment. Ciclopirox was rapidly absorbed and cleared with a short half-life. Plasma concentrations of an inactive ciclopirox glucuronide metabolite were greater than those of ciclopirox. Repression of survivin expression was observed in peripheral blood cells isolated from patients treated once daily with ciclopirox olamine at doses greater than 10 mg/m(2) , demonstrating biological activity of the drug. Dose-limiting gastrointestinal toxicities were observed in patients receiving 80 mg/m(2) four times daily, and no dose limiting toxicity was observed at 40 mg/m(2) once daily. Hematologic improvement was observed in two patients. Once-daily dosing of oral ciclopirox olamine was well tolerated in patients with relapsed or refractory hematologic malignancies, and further optimization of dosing regimens is warranted in this patient population.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.