bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interactions between xenoestrogens and ketoconazole on hepatic CYP1A and CYP3A, in juvenile Atlantic cod (Gadus morhua)
Authors: Hasselberg Linda , Grøsvik Bjørn E , Goksøyr Anders , Celander Malin C 
Published: February 2005

Abstract
Background
Xenoestrogens and antifungal azoles probably share a common route of metabolism, through hepatic cytochrome P450 (CYP) enzymes. Chemical interactions with metabolic pathways may affect clearance of both xenobiotics and endobiotics. This study was carried out to identify possible chemical interactions by those substances on CYP1A and CYP3A, in Atlantic cod liver. We investigated effects of two xenoestrogens (nonylphenol and ethynylestradiol) and of the model imidazole ketoconazole, alone and in combination.

Results
Treatment with ketoconazole resulted in 60% increase in CYP1A-mediated ethoxyresorufin-O-deethylase (EROD) activity. Treatment with nonylphenol resulted in 40% reduction of CYP1A activity. Combined exposure to ketoconazole and nonylphenol resulted in 70% induction of CYP1A activities and 93% increase in CYP1A protein levels. Ketoconazole and nonylphenol alone or in combination had no effect on CYP3A expression, as analyzed by western blots. However, 2-dimensional (2D) gel electrophoresis revealed the presence of two CYP3A-immunoreactive proteins, with a more basic isoform induced by ketoconazole. Treatment with ketoconazole and nonylphenol alone resulted in 54% and 35% reduction of the CYP3A-mediated benzyloxy-4-[trifluoromethyl]-coumarin-O-debenzyloxylase (BFCOD) activity. Combined exposure of ketoconazole and nonylphenol resulted in 98% decrease in CYP3A activity. This decrease was greater than the additive effect of each compound alone. In vitro studies revealed that ketoconazole was a potent non-competitive inhibitor of both CYP1A and CYP3A activities and that nonylphenol selectively non-competitively inhibited CYP1A activity. Treatment with ethynylestradiol resulted in 46% decrease in CYP3A activity and 22% decrease in protein expression in vivo. In vitro inhibition studies in liver microsomes showed that ethynylestradiol acted as a non-competitive inhibitor of CYP1A activity and as an uncompetitive inhibitor of CYP3A activity.

Conclusions
Ketoconazole, nonylphenol and ethynylestradiol all interacted with CYP1A and CYP3A activities and protein expression in Atlantic cod. However, mechanisms of interactions on CYP1A and CYP3A differ between theses substances and combined exposure had different effects than exposure to single compounds. Thus, CYP1A and CYP3A mediated clearance may be impaired in situations of mixed exposure to those types of compounds.
A conditional-lethal vaccinia virus mutant demonstrates that the I7L gene product is required for virion morphogenesis
Authors: Byrd Chelsea M , Hruby Dennis E 
Published: February 2005

AbstractA conditional-lethal recombinant virus was constructed in which the expression of the vaccinia virus I7L gene is under the control of the tetracycline operator/repressor system. In the absence of I7L expression, processing of the major VV core proteins is inhibited and electron microscopy reveals defects in virion morphogenesis subsequent to the formation of immature virion particles but prior to core condensation. Plasmid-borne I7L is capable of rescuing the growth of this virus and rescue is optimal when the I7L gene is expressed using the authentic I7L promoter. Taken together, these data suggest that correct temporal expression of the VV I7L cysteine proteinase is required for core protein maturation, virion assembly and production of infectious progeny.
Role of Pentoxifylline and Vitamin E in Attenuation of Radiation-Induced Fibrosis
Authors: Chiao Teresa B , Lee Audrey J 
Published: February 2005

OBJECTIVE: To evaluate the use of pentoxifylline and vitamin E as monotherapy and in combination for the treatment of radiation-induced fibrosis (RIF). DATA SOURCES: Literature retrieval was performed through MEDLINE (1966–March 2004) using the terms vitamin E, α-tocopherol, pentoxifylline, radiation-induced fibrosis, and radiation injury. DATA SYNTHESIS: Few treatments exist for managing RIF of soft tissues. Due to its antioxidant properties, vitamin E may reduce the oxidative damage induced by radiation. The precise mechanism of action for pentoxifylline in management of RIF remains unclear. Uncontrolled studies evaluating vitamin E or pentoxifylline as monotherapy in RIF have shown modest improvement in clinical regression of fibrosis. However, controlled data are needed to verify these benefits. Studies involving pentoxifylline plus vitamin E demonstrated regression in RIF. The combination was more effective than placebo and may be superior to monotherapy with either agent. Adverse effects were rarely reported in the studies and consisted mainly of gastrointestinal and nervous system effects. CONCLUSIONS: Overall, pentoxifylline is well tolerated and is one of the few commercially available drugs with clinical data for management of RIF. Despite a lack of large, well-designed clinical trials, pentoxifylline plus vitamin E should be considered as an option in patients with symptomatic RIF.
Hyperglycemia in the Hospital Setting: The Case for Improved Control among Non-Diabetics
Authors: Conner Therese M , Flesner-Gurley Kelly R , Barner Jamie C 
Published: February 2005

OBJECTIVE: To review studies on the role of hyperglycemia in acutely ill adults, regardless of diabetes diagnosis, and the impact of glucose control on health outcomes. DATA SOURCES: Searches on Ovid MEDLINE, Ovid Evidence-Based Medicine (EBM), and PubMed MEDLINE, limited to articles written in English, trials conducted on adult subjects, and material published between 1994 and April 2004. Search words included the major MeSH term hyperglycemia and title words glucose, hyperglycemia/hyperglycemic, or insulin therapy, with text words admission, hospitalized, inhospital, or inpatient. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated, and all information deemed relevant was included in this review. DATA SYNTHESIS: Hyperglycemia, even in patients without diabetes, has been shown to be detrimental among inpatients in medical and surgical units, as well as in critical care. A review of 25 outcomes studies indicated that the majority of research on this topic used retrospective or prospective cohort designs; only 2 were conducted as randomized controlled studies. In general, the findings demonstrated negative impact on outcomes among various patient populations with hyperglycemia including increased lengths of stay, health complications, utilization of resources, and risk of mortality. CONCLUSIONS: Studies report that hyperglycemia is a common but detrimental condition and that better control in the hospital setting decreases short- and long-term risk of mortality, illness complications, hospital lengths of stay, and healthcare costs. Increased efforts to treat hyperglycemia and screen for diabetes are needed in the hospital setting. Future studies on cost-effective approaches to glucose control are recommended.
Adverse Drug Reaction and Medication Error Reporting by Pharmacy Students
Authors: Sears Erin L , Generali Joyce A 
Published: February 2005

BACKGROUND: The reporting of adverse drug reactions (ADRs) and medication errors is the responsibility of all who are involved, particularly pharmacists. Since pharmacists are often privy to information surrounding ADRs and medication errors, it is of utmost importance that they are educated regarding the procedures of reporting. OBJECTIVE: To determine pharmacy students' knowledge of and ability to report ADRs and medication errors. METHODS: A total of 1322 students from 9 colleges of pharmacy were surveyed. RESULTS: The largest group of respondents was fifth-year pharmacy students (38%) followed by third-, fourth-, and sixth-year students (28%, 26%, and 8%, respectively). The majority of students reported learning about ADR and medication error reporting programs via didactic experiences. In comparison, fewer students cited alternative mechanisms of learning, including experiential rotations and work experience. Overall, respondents demonstrated the most experience with MedWatch and the least experience with the Vaccine Adverse Event Reporting System (VAERS). As students progressed through pharmacy curricula, there was a positive trend in the ability to locate and complete MedWatch forms. For VAERS and Medication Error Reporting (MER) program forms, however, this positive trend was broken at year 4. For all programs, significantly fewer students demonstrated appropriate use of the forms compared with those indicating familiarity with the programs. CONCLUSIONS: This study demonstrated that students are becoming familiar with ADR and MER programs via the college curriculum; however, there is opportunity for greater exposure and understanding. Colleges of pharmacy should continually seek methods to strengthen the education provided to pharmacy students regarding these programs.
Dramatic Improvement in down Syndrome—Associated Cognitive Impairment with Donepezil
Authors: Kondoh Tatsuro , Amamoto Nagisa , Doi Tomoki , Hamada Hitomi , Ogawa Yoji , Nakashima Mikiro , Sasaki Hitoshi , Aikawa Katsuyo , Tanaka Tatsuhiko , Aoki Mizue , Harada Junji , Moriuchi Hiroyuki 
Published: February 2005

OBJECTIVE: To report 2 cases of patients with Down syndrome and severe cognitive impairment who gained dramatic improvements in quality of life (QOL) upon donepezil treatment. CASE SUMMARIES: Case 1. A 38-year-old woman with Down syndrome, diagnosed with secondary progressive dementia when her mental state had deteriorated rapidly after graduation from junior high school, started donepezil treatment. The loading dose was 3 mg/day and was increased to 5 mg/day for maintenance. One month after the dose was increased, adverse effects such as soft stool and urinary incontinence appeared. These adverse effects disappeared when the dose was decreased again to 3 mg/day. Her QOL improved dramatically with this minimal dose. She recovered verbal and written communication skills that she had lost for the past 21 years. Case 2. A 22-year-old man with Down syndrome, who had been diagnosed as having severe mental retardation, was put on donepezil therapy. Both loading and maintenance doses were 3 mg/day. His QOL had also dramatically improved, with some recovery in verbal communication. Transient agitation/violence and transient muscle weakness appeared during the first few months of treatment. DISCUSSION: Patients with Down syndrome may be more sensitive to donepezil therapy than others and may benefit from this medicine, although they may also have adverse effects more frequently. CONCLUSIONS: Donepezil may be a useful medicine for some patients with Down syndrome with severe cognitive impairment or mental retardation if the adverse effects are manageable.
Clarithromycin—Nifedipine Interaction as Possible Cause of Vasodilatory Shock
Authors: Gerónimo-Pardo Manuel , Cuartero-del-Pozo Ana B , Jiménez-Vizuete José M , Cortiñas-Sáez Manuel , Peyró-García Ramón 
Published: February 2005

OBJECTIVE: To report a case of vasodilatory shock possibly resulting from a clarithromycin—nifedipine interaction. CASE SUMMARY: A 77-year-old male with uncontrollable hypertension developed shock, heart block, and multiorgan failure 2 days after clarithromycin was added to his antihypertensive treatment (nifedipine, captopril, doxazosin). Invasive monitoring revealed hyperdynamic shock with decreased systemic vascular resistances. DISCUSSION: Nifedipine is metabolized by isoenzyme CYP3A4. This metabolic pathway is inhibited by clarithromycin, thus potentially increasing the plasma nifedipine concentration, which may lead to excessive calcium-channel blocker effects. Clinical manifestations of excessive calcium-channel blockade comprise hypotension or vasodilatory shock and heart block, as in our case. An objective causality assessment revealed that this drug interaction was the possible cause of these adverse effects. Because of an initial diagnosis of septic shock, suspicion of this entity was delayed and specific diagnostic and treatment were not possible. CONCLUSIONS: This life-threatening clinical picture, including shock and heart block, was possibly the result of a pharmacokinetic interaction between clarithromycin and nifedipine.
Impact of Topiramate on Serum Bicarbonate Concentrations in Adults
Authors: Garris Shauna S , Oles Karen S 
Published: February 2005

BACKGROUND: Topiramate is an antiepileptic medication with multiple pharmacologic effects, including inhibition of carbonic anhydrase activity. It is associated with metabolic acidosis in both children and adults. OBJECTIVE: To evaluate the incidence and magnitude of the effect of topiramate on serum bicarbonate concentrations in an adult population. METHODS: This was a retrospective cohort study. Data were evaluated to assess the relationship between serum bicarbonate concentrations before and during topiramate therapy. RESULTS: Fifty-four patients (40 females) with a mean age of 47.6 years (range 19–89) were included in the study. Mean ± SD serum bicarbonate concentrations before and during topiramate therapy were 26.8 ± 2.9 mEq/L (range 21–36) and 21.7 ± 3.6 mEq/L (range 13–29), respectively, with a mean difference of 5.1 (95% CI 3.7 to 6.5; p < 0.001). Twenty-six patients (48%) had low serum bicarbonate concentrations while on topiramate, with a mean concentration of 18.8 mEq/L (range 13–21). CONCLUSIONS: Topiramate was associated with metabolic acidosis in 48% of the patients studied, which did not result in clinically significant problems.
Caring for Poorly Controlled Diabetes Mellitus: A Randomized Pharmacist Intervention
Authors: Odegard Peggy S , Goo Alvin , Hummel Jeff , Williams Kristal L , Gray Shelly L 
Published: February 2005

BACKGROUND: There is limited information from randomized controlled studies about the influence of pharmacist interventions on diabetes control. OBJECTIVE: To evaluate the effect of a pharmacist intervention on improving diabetes control; secondary endpoints were medication appropriateness and self-reported adherence. METHODS: A randomized, controlled, multi-clinic trial was conducted in the University of Washington Medicine Neighborhood Clinics. Seventy-seven subjects, ⩾18 years old with a hemoglobin (Hb) A1c ⩾9% at baseline and taking at least one oral diabetes medication, were randomized to receive a pharmacist intervention (n = 43) or usual care (n = 34) for 6 months followed by a 6-month usual-care observation period for both groups. Subjects met with a clinical pharmacist to establish and initiate a diabetes care plan followed by weekly visits or telephone calls to facilitate diabetes management and adherence. HbA1c, medication appropriateness, and self-reported adherence were assessed at baseline, 6 months, and 12 months. RESULTS: The mean HbA1c did not differ between groups over the 12-month period (p = 0.61). A reduction in HbA1c was noted for both groups over time compared with baseline (p = 0.001); however, control subjects relied more heavily on provider visits. Medication appropriateness was not improved for diabetes medications (p = 0.65). Self-reported adherence was not significantly improved by the intervention. CONCLUSIONS: This pharmacist intervention did not significantly improve diabetes control, but did allow for similar HbA1c control with fewer physician visits. Medication appropriateness and self-reported adherence compared with usual care in individuals with poorly controlled diabetes were not changed.
Refractory Anaphylactic Shock Associated with Ketoconazole Treatment
Authors: Liu Ping-Yen , Lee Cheng-Han , Lin Li-Jen , Chen Jyh-Hong 
Published: February 2005

OBJECTIVE: To report a rare but severe reaction of refractory anaphylactic shock with ketoconazole treatment—associated hypotensive episodes in an elderly patient. CASE SUMMARY: A 72-year-old woman received antifungal therapy for her almost completely occluded cornea infected with Candida albicans. She was initially prescribed oral ketoconazole 200 mg twice daily. She developed hypotension over the first 2 days of therapy (BP 136/82 mm Hg at baseline; 90/50 mm Hg on day 2). Severe hypotension (BP 90/49 mm Hg) unresponsive to fluid therapy or high-dose dopamine developed on day 4 of therapy. An invasive Swan—Ganz catheterization study showed a very low level of peripheral vascular resistance with high cardiac output index without clinical signs of infection. When laboratory tests showed a high level of plasma tryptase, anaphylactic redistribution shock was diagnosed. Her vital signs became more stable after treatment with hydrocortisone and epinephrine infusion. She was discharged in good condition after 24 hours of observation. DISCUSSION: As of December 2004, refractory anaphylactic shock resulting from ketoconazole use had not been reported. The events of hypotension were strongly associated with the intake of ketoconazole. The hemodynamic results obtained with Swan—Ganz catheterization were compatible with anaphylactic shock. The Naranjo probability scale showed a probable association of the adverse event with ketoconazole. CONCLUSIONS: Ketoconazole may cause severe anaphylactic shock even when taken orally. Invasive catheterization and elevated tryptase levels can provide important information in the management of anaphylactic shock.
Angiotensin Receptor Blockers versus ACE Inhibitors: Prevention of Death and Myocardial Infarction in High-Risk Populations
Authors: Epstein Benjamin J , Gums John G 
Published: February 2005

OBJECTIVE: To determine, through a review of the medical literature, whether there is adequate evidence to support the use of angiotensin receptor blockers (ARBs) in place of angiotensin-converting enzyme (ACE) inhibitors in high-risk populations, focusing on the prevention of death and myocardial infarction (MI). DATA SOURCES: Original investigations, reviews, and meta-analyses were identified from the biomedical literature via a MEDLINE search (1966–August 2004). Published articles were also cross-referenced for pertinent citations, and recent meeting abstracts were searched for relevant data. STUDY SELECTION AND DATA EXTRACTION: All articles identified during the search were evaluated. Preference was given to prospective, randomized, controlled trials that evaluated major cardiovascular endpoints and compared ARBs with ACE inhibitors, active controls, or placebo. DATA SYNTHESIS: The renin—angiotensin system plays a pivotal role in the continuum of cardiovascular disease and represents a major therapeutic target in the treatment of patients at risk for vascular events. While ACE inhibitors have been definitively shown to prevent death and MI, studies with ARBs in similar populations have not reduced these endpoints. In clinical trials that enrolled patients with heart failure, post-MI, diabetes, and hypertension, ARBs did not prevent MI or prolong survival compared with ACE inhibitors, other antihypertensives, or placebo. CONCLUSIONS: ACE inhibitors and ARBs should not be considered interchangeable, even among patients with a documented history of ACE inhibitor intolerance. ARBs can be considered a second-line alternative in such patients with the realization that they have not been shown to prevent MI or prolong survival.
Improvement of Dry Mouth by Replacing Paroxetine with Fluvoxamine
Authors: Arima Yuka , Kubo Chiharu , Tsujimoto Masayuki , Ohtani Hisakazu , Sawada Yasufumi 
Published: February 2005

OBJECTIVE: To present a case of improvement of paroxetine-induced dry mouth by substitution of fluvoxamine and analyze this case based on receptor occupancy theory. CASE SUMMARY: A 66-year-old woman with major depressive disorder had been treated with brotizolam 0.5 mg/day, flunitrazepam 2 mg/day, sulpiride 100 mg/day, bromazepam 2 mg/day, trazodone 25 mg/day, and paroxetine hydrochloride 10 mg/day. Although her psychological symptoms improved gradually, she complained of dry mouth. Paroxetine was replaced with fluvoxamine maleate 50 mg/day, and the dryness disappeared within a month. DISCUSSION: We calculated the time courses of muscarinic acetylcholine (mACh) receptor occupancy after oral administration of paroxetine and fluvoxamine at the treatment doses by using pharmacokinetic parameters obtained from the literature. The mACh receptor occupancy was estimated to be decreased from 0.22% to 0.020% by replacing paroxetine with fluvoxamine. CONCLUSIONS: The improvement of dry mouth observed after the replacement of paroxetine with fluvoxamine in this patient may have been due to a decrease in the mACh receptor occupancy.
Perceived Risk of Chlamydial and Gonococcal Infection Among Sexually Experienced Young Adults In the United States
Authors: Ford Carol A. , Jaccard James , Millstein Susan G. , Bardsley Philip E. , Miller William C. 
Published: February 2005

CONTEXT: Understanding young adults' perceived risk of chlamydial and gonococcal infection can inform interventions to reduce the prevalence of these sexually transmitted diseases.METHODS: Bivariate and multivariate analyses, using data from Wave 3 of the National Longitudinal Study of Adolescent Health (2001–2002), were conducted to examine relationships between perceived risk and selected characteristics in two groups: a nationally representative sample of sexually experienced 18–26‐year‐olds and a subsample of those who tested positive for chlamydia or gonorrhea. The relationship between current infection and perceived risk was also evaluated.RESULTS: Only 14% of all respondents and 33% of infected participants reported some perceived risk of chlamydial or gonococcal infection. In the overall sample, the odds of perceiving risk were significantly elevated among blacks, His‐panics, unmarried respondents, inconsistent condom users and nonusers, respondents who reported multiple partners in the past year, those who had received a diagnosis of chlamydia or gonorrhea in the past year, and those reporting current symptoms (odds ratios, 1.5–3.3). Currently infected participants were significantly more likely than those who were not infected to perceive some risk of infection (2.4). Among infected respondents, the factors positively associated with perceived risk were being black or Hispanic, using condoms inconsistently or not using them, having exchanged money for sex, having been tested in the past year but with no diagnosis, having received a diagnosis, and reporting current symptoms (2.5–5.2).CONCLUSIONS: Interventions to increase the accuracy of young adults' risk perceptions may influence sexual and health care‐seeking behaviors in a way that will reduce rates of chlamydia and gonorrhea.
Enhanced Temporal Response Properties of Anteroventral Cochlear Nucleus Neurons to Broadband Noise
Authors: Louage Dries H. G. , van der Heijden Marcel , Joris Philip X. 
Published: February 2005

Compared with auditory nerve (AN) fibers, trapezoid body (TB) fibers of the cat show enhanced synchronization to low-frequency tones. This phenomenon probably contributes to the high temporal resolution of binaural processing. We examined whether enhanced synchronization also occurs to sustained broadband noise. We recorded responses to a reference Gaussian noise and its polarity-inverted version in the TB of barbiturate-anesthetized cats. From these we constructed shuffled autocorrelograms (SACs) and quantified spike timing by measuring the amplitude and width of their central peak.Many TB fibers with low characteristic frequency (CF) showed SACs with higher and narrower central peaks than ever observed in the AN, indicating better consistency and precision of temporal coding. Larger peaks were also observed in TB fibers with high CF, but this was mostly caused by higher average firing rates, resulting in a larger number of coincident spikes across stimulus repetitions. The results document monaural preprocessing of the temporal information delivered to binaural nuclei in the olivary complex, which likely contributes to the high sensitivity to interaural time differences.