bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ameliorative effect of cysteine prodrug l‐2‐oxothiazolidine‐4‐carboxylic acid on cisplatin‐induced nephrotoxicity in rats
Authors: Ali B.H. , Al Moundhri M.S. , Tag Eldin M. , Nemmar A. , Tanira M.O. 
Published: September 2007

AbstractPathogenesis of nephrotoxicity of the synthetic anticancer drug cisplatin (CP) involves generation of reactive oxygen species and free radicals in the kidney cortex, and cysteine prodrug l‐2‐oxothiazolidine‐4‐carboxylic acid (OTC) has been confirmed to have a strong antioxidant action. Therefore, in the present work, we aimed at testing the possible protective or palliative effect of OTC on CP nephrotoxicity in rats. OTC was given at an oral dose of 150 mg/kg/day for 7 days. On day 7, some of these rats were given a single intraperitoneal injection of CP (or vehicle) at a dose of 6 mg/kg. Rats were killed, blood and urine samples were collected, and the kidneys were removed 6 days after CP treatment. Nephrotoxicity was evaluated histopathologically by light microscopy, and biochemically by measuring the concentrations of creatinine and urea in serum, reduced glutathione (GSH) concentration and superoxide dismutase (SOD) activity in renal cortex, and by urinalyses. CP significantly increased the concentrations of urea and creatinine (P < 0.05) by about 128% and 170% respectively. CP treatment reduced cortical GSH concentration by about 34% (P < 0.05), and the activity of SOD by about 28% (P < 0.05). CP treatment significantly increased urine volume and N‐acetyl‐β‐d‐glucosaminidase (NAG) activity, and significantly decreased osmolality and protein concentrations. OTC significantly mitigated all these effects. Sections from saline‐ and OTC‐treated rats showed apparently normal proximal tubules. However, kidneys of CP‐treated rats had a moderate degree of necrosis. This appeared to be lessened when CP was given simultaneously with OTC. The concentration of CP in the cortical tissues was not significantly altered by OTC treatment. The results suggested that OTC had ameliorated the histopathological and biochemical indices of nephrotoxicity in rats. Pending further pharmacological and toxicological studies, OTC may potentially be useful as a nephroprotective agent.
Amine oxidases and monooxygenases in the in vivo metabolism of xenobiotic amines in humans: has the involvement of amine oxidases been neglected?
Authors: Strolin Benedetti Margherita , Tipton Keith F. , Whomsley Rhys 
Published: September 2007

AbstractIn this review, the major enzyme systems involved in vivo in the oxidative metabolism of xenobiotic amines in humans are discussed, i.e. the monooxygenases [cytochrome P450 system (CYPs) and flavin‐containing monooxygenases (FMOs)] and the amine oxidases (AOs). Concerning the metabolism of xenobiotic amines (drugs in particular) by monoamine oxidases (MAOs), this aspect has been largely neglected in the past. An exception is the extensive investigation carried out on the inhibition of the metabolism of tyramine, when tyramine‐containing food is ingested by subjects taking inhibitors of MAO A or of both MAO A and B. Moreover, investigations in humans on the metabolism of drug amines on the market by AOs, such as semicarbazide‐sensitive amine oxidases (SSAOs) and polyamine oxidases (PAOs), are practically nonexistent, with the exception of amlodipine. In contrast to MAOs, monooxygenases (CYP isoenzymes more than FMOs) have been extensively investigated concerning their involvement in the metabolism of xenobiotics. It is possible that the contribution of AOs to the overall metabolism of xenobiotic amines in humans is underestimated or erroneously estimated, as most investigations of drug metabolism are performed using in vitro test systems optimized for CYP activity, such as liver microsomes, and most investigations of drug metabolism in vivo in humans carry out only the identification of the final, stable metabolites. However, for some drugs on the market, the involvement of MAOs in their in vivo metabolism in humans has been demonstrated recently, among these drugs citalopram, sertraline and the triptans are examples that can be mentioned.
Synergistic interaction between dexamethasone and tramadol in a murine model of acute visceral pain
Authors: Dürsteler Christian , Miranda Hugo F. , Poveda Raquel , Mases Anna , Planas Eulalia , Puig Margarita M. 
Published: September 2007

AbstractTramadol is effective in the management of mild to moderate postoperative pain, but its administration is associated with nausea and vomiting. Patients treated with tramadol, often receive dexamethasone as antiemetic. The aim of our investigation was to assess if the two drugs interact in a murine model of acute visceral pain. Using the acetic acid writhing test in mice, we assessed the antinociceptive effects of tramadol and dexamethasone (a glucocorticoid with antiemetic effect) administrated individually and in a 1 : 1 fixed ratio combination. Tramadol and dexamethasone induced a dose‐dependent inhibition of the writhing response when administered individually, with ED50values of 2.9 [2.09–4.31, 95% confidence limit (CL)] mg/kg, and 0.13 (0.05–0.29, 95% CL) mg/kg, respectively. The ED50of the combination was 0.13 (0.01–0.29, 95% CL) mg/kg; the isobolographic and interaction index analysis revealed a synergistic interaction. The results suggest that the combination of tramadol and dexamethasone could be beneficial in the management of postoperative pain in humans.
Protective effect of rutin, a polyphenolic flavonoid against haloperidol‐induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical changes
Authors: Bishnoi Mahendra , Chopra Kanwaljit , Kulkarni Shrinivas K. 
Published: September 2007

AbstractThe occurrence and irreversibility of tardive dyskinesia (TD), a motor disorder of the orofacial region, resulting from chronic neuroleptic treatment has been considered a major clinical issue in the treatment of schizophrenia. The molecular mechanism underlying the pathophysiology of TD is not completely known. Several animal studies have demonstrated an enhancement of oxidative damage and increased glutamatergic transmission after chronic administration of neuroleptics. The present study investigated the effect of rutin, an antioxidant in haloperidol‐induced orofacial dyskinesia by using different behavioural (orofacial dyskinetic movements, stereotypic rearing, locomotor activity, percent retention), biochemical [lipid peroxidation, reduced glutathione levels, antioxidant enzyme levels (SOD and catalase)] and neurochemical (neurotransmitter levels) parameters. Chronic administration of haloperidol (1 mg/kg i.p. for 21 days) significantly increased vacuous chewing movements, tongue protrusions and facial jerking in rats, which were significantly inhibited by rutin. Chronic administration of haloperidol also resulted in dopamine receptor sensitivity as evident by a well‐shaped response (initial decrease followed by increase) in locomotor activity and stereotypic rearing and also decreased percent retention time on elevated plus maze paradigm. Pretreatment with rutin reversed these behavioural changes. Besides, haloperidol also induced oxidative damage in all regions of brain which was prevented by rutin, especially in the subcortical region containing striatum. Although turnover of dopamine and noradrenaline decreased in both cortical and subcortical regions after chronic administration of haloperidol, it was significantly reversed by high‐dose rutin treatment. The findings of the present study suggested the involvement of free radicals in the development of neuroleptic‐induced orofacial dyskinesia, a putative model of TD, and rutin as a possible therapeutic option to treat this hyperkinetic movement disorder.
Pharmacological evidence of calcium‐channel blockade by essential oil of Ocimum gratissimum and its main constituent, eugenol, in isolated aortic rings from DOCA‐salt hypertensive rats
Authors: Interaminense Leylliane Fátima Leal , Jucá Davi Matthews , Magalhães Pedro Jorge Caldas , Leal‐Cardoso José Henrique , Duarte Gloria Pinto , Lahlou Saad 
Published: September 2007

AbstractIntravenous (i.v.) treatment of conscious DOCA‐salt hypertensive rats with the essential oil of Ocimum gratissimum L. (Labiatae) (EOOG) induced a hypotensive effect that seems related to an active vascular relaxation rather than withdrawal of sympathetic tone. To corroborate this hypothesis, the present study examined the vascular effects of EOOG and its main constituent, eugenol (EUG) and the putative mechanisms underlying these effects. Additionally, the role of the vascular β2‐adrenergic mechanism in the mediation of EOOG‐induced hypotension has also been investigated. In conscious DOCA‐salt hypertensive rats, the EOOG‐induced hypotension was reversible and remained unchanged by i.v. pretreatment with propranolol (2 mg/kg). In isolated aorta preparations with intact endothelium from DOCA‐salt hypertensive rats, EOOG (1–1000 μg/mL) and EUG (0.006–6 mm) relaxed the phenylephrine‐induced contraction similarly with IC50 [geometric mean (95% confidence interval)] values of 226.9 (147.8–348.3) μg/mL and 1.2 (0.6–2.1) mm, respectively. Vasorelaxant effects of EOOG were significantly altered by removal of the vascular endothelium [IC50 = 417.2 (349.5–497.8) μg/mL]. In a calcium‐free medium, the CaCl2‐induced contractions were significantly reduced and even abolished by EOOG at 300 and 1000 μg/mL, respectively, whereas EOOG (1000 μg/mL) did not have any significant effect on caffeine‐induced contractions. Similar results were obtained with EUG (1.8 and 6 mm) on both CaCl2‐ and caffeine‐induced contractions, respectively. The data suggest that hypotensive responses to EOOG in DOCA‐salt hypertensive rats are due to an active vascular relaxation, which is partly dependent upon the integrity of the vascular endothelium and seems predominantly mediated through an inhibition of plasmalemmal Ca2+ influx rather than Ca2+‐induced Ca2+ release from the sarcoplasmic reticulum.
Impact of Multitiered Copayments on the Use and Cost of Prescription Drugs among Medicare Beneficiaries
Authors: Gilman Boyd H. , Kautter John 
Published: September 2007

Objectives. To assess the impact of multitiered copayments on the cost and use of prescription drugs among Medicare beneficiaries.Data Sources. Marketscan 2002 Medicare Supplemental and Coordination of Benefits database and Plan Benefit Design database.Study Design. The study uses cross‐sectional variation in copayment structures among firms with a self‐insured retiree health plan to measure the impact of number of copayment tiers on total and enrollee drug payments, number of prescriptions filled, and generic substitution. The study also assesses the effect of enrollee cost sharing on the cost and use of prescription medications for the long‐term treatment of chronic conditions.Data Collection Methods. We linked plan enrollment and benefit data with medical and drug claims for 352,760 Medicare beneficiaries with employer‐sponsored retiree drug coverage.Primary Findings. Medicare beneficiaries in three‐tiered plans had 14.3 percent lower total drug expenditures, 14.6 percent fewer prescriptions filled, and 57.6 percent higher out‐of‐pocket costs than individuals in lower tiered plans. They also had fewer brand name and generic prescriptions filled, and a higher percentage of generics. The estimated price elasticity of demand for prescription drug expenditures was −0.23. Finally, for maintenance medications used for the long‐term treatment of chronic conditions, members in three‐tiered plans had 11.5 percent fewer prescriptions filled.Conclusions. Higher tiered drug plans reduce overall expenditures and the number of prescriptions purchased by Medicare beneficiaries. Beneficiaries are less responsive to cost sharing incentives when using drugs to treat chronic conditions.
Identifying Persons with Treated Asthma Using Administrative Data via Latent Class Modelling
Authors: Prosser Robert J. , Carleton Bruce C. , Smith M. Anne 
Published: September 2007

Objective. To develop a parsimonious model of the respiratory patient population in British Columbia (BC), Canada through latent class modelling (LCM), using administrative data records and to assess conventional case definitions for asthma in relation to model‐based case selection.Data Sources. 1996–2001 data from linked provincial databases containing fee‐for‐service physician billing records, hospital inpatient separation abstracts, and prescription drug purchase records for 1.9 million BC respiratory patients.Study Design. This is a retrospective methodological/descriptive study that assesses case definitions for asthma in terms of sensitivity and specificity using a model fitted to seven physician, hospital and medication utilization markers in place of a conventional gold standard.Data Collection. We computed values of the treatment markers for each of the 5 years for each patient aged 5–55 years who had had at least one occurrence of a respiratory diagnosis code.Principal Findings. The marker for prescription of short‐acting β agonists (SABAs) consistently had the highest sensitivity. Markers' specificities ranged from 0.97 to 1.0. The conventional case definitions' sensitivities were 0.41–0.87; specificities ranged from 0.98 to 0.997. Model‐based estimates of asthma prevalence increased from 827/10,000 in 1996 to 992/10,000 in 2001. Conventional case definitions' estimates were consistently lower.Conclusions. The linkage between utilization and case status is more complex than conventional case definitions allow for. LCM‐based case classification was consistent over time and tends to lead to larger prevalence estimates than conventional definitions. The estimated increases in asthma prevalence are reliable. LCM provides health services planners with a useful probability‐based approach for developing and assessing case definitions and estimating case prevalence.
Risks and Causes of Hospitalizations among Physicians in Taiwan
Authors: Lin Chi‐Miao , Yang Chiang‐Hsing , Sung Fung‐Chang , Li Chung‐Yi 
Published: September 2007

Objectives. To assess the causes and cause‐specific risks of hospitalization among physicians in Taiwan.Data Source. The data used in this study were retrieved from filed claims and registries of the National Health Insurance Research Database. A cohort of 33,380 physicians contracted with the national insurance program between 1997 and 2002 were linked to the information on the inpatient claim data for hospitalization.Study Design. The physicians' incidence density of hospitalization was compared with that of the general population, other health personnel, and nurses to compute the calendar year‐, age‐, and gender‐standardized hospitalization ratios (SHRs). A multivariate log‐linear model was also used to assess the effects of gender, age, type of contract, and specialty on the risks of hospitalization.Principal Findings. Compared with the general population, physicians experienced significantly reduced risks of all causes (SHR=54.5, 95 percent confidence interval [CI] 53.4–55.5) and all major cause‐specific hospitalizations, especially mental disorders (SHR=6.9, 95 percent CI 5.8–8.4). On the other hand, compared with other health personnel, physicians had a small but significantly higher risk of all causes of hospitalization (SHR=107.8, 95 percent CI 105.1–110.6). Higher risks of hospitalization were also noted for neoplasms (SHR=108.9, 95 percent CI 102.0–116.3) and diseases of the respiratory system (SHR=114.2, 95 percent CI 107.3–121.5). In addition to the above diagnoses, physicians also had significantly higher risks for genitourinary and musculoskeletal system and connective tissue problems than nurses. Compared with their physician colleagues, female physicians, young (<30 years) and older (≥60 years) physicians, and those working with the health institutions and programs were at elevated risks of hospitalization for all causes as well as for certain specific diseases.Conclusions. Physicians in Taiwan are at higher risks of developing specific diseases compared with their allied health colleagues. As the health of physicians is vital to the quality of care, Taiwanese health policy analysts should recognize that increased patient volume and satisfaction with public health care should not be achieved at the expense of physicians' health.
The Effect of Premium Changes on SCHIP Enrollment Duration
Authors: Herndon Jill Boylston , Vogel W. Bruce , Bucciarelli Richard L. , Shenkman Elizabeth A. 
Published: September 2007

Research Objective. To examine the impact of premium changes in Florida's State Children's Health Insurance Program (SCHIP) on enrollment duration.Data Sources. Administrative records, containing enrollment and demographic data, were used to identify 173,330 enrollment spells for 153,768 children in Florida's SCHIP from July 2002 through June 2004. Health care claims data were used to classify the children's health status.Study Design. Accelerated failure time models were used to examine the immediate and longer term effects on enrollment length of a temporary premium increase of $15 to $20 per family per month (PFPM) for children in families with income between 101–150 percent of the federal poverty level (FPL) and a permanent premium increase of $15 to $20 PFPM for children in families with 151–200 percent FPL. Health status and sociodemographic variables were included as covariates. Transfers to other public health insurance programs were taken into account.Principal Findings. Enrollment lengths decreased significantly immediately following the premium increases, with a greater percentage decrease among lower income children (61 percent) than higher income children (55 percent). Enrollment lengths partially recovered in the longer term for both the temporary and permanent changes. Those with significant acute or chronic health conditions had longer enrollment lengths and were less sensitive to premium changes than healthy children.Conclusions. An increase in the PFPM premium amount had differential effects across income categories and health status levels. Enrollment lengths remained shortened after the premium increase was rescinded for lower income families, suggesting that it may be difficult to reverse the impacts of even a short‐term premium increase.
Program Structure and Counselor–Client Contact in Outpatient Substance Abuse Treatment
Authors: Knight Danica K. , Broome Kirk M. , Simpson D. Dwayne , Flynn Patrick M. 
Published: September 2007

Objectives. To examine organizational structural attributes associated with counselor–client contact.Data Sources. Data were collected in 2004 and 2005 for a federally funded project, which simultaneously examines organizational structure, functioning, and resources among outpatient substance abuse treatment programs.Study Design. The study uses a naturalistic design to investigate organizational structure measures—ownership, accreditation, and supplemental services—as predictors of time in counseling and case management, and caseload size, controlling for geographic differences.Data Collection. Directors at 116 outpatient drug‐free treatment programs located in four regions across the U.S. (Great Lakes, Gulf Coast, Northwest, and Southeast) voluntarily completed a survey about program structure.Primary Findings. Clients received more counseling hours in programs that were “intensive,” publicly owned, accredited, and had a lower proportion of recently hired counselors. More case management hours were offered in “intensive,” private‐for‐profit or publicly owned (versus private‐nonprofit) programs, serving a lower proportion of dual‐diagnosis clients, and providing more on‐site supplemental services. Smaller caseloads were found in programs that were accredited and had a smaller average client census and a lower proportion of criminal justice referred clients.Conclusions. Organizational attributes are related to counselor–client contact and may have implications for staff turnover and service quality.
Drug Use Patterns in Severely Mentally Ill Medicare Beneficiaries: Impact of Discontinuities in Drug Coverage
Authors: Simoni‐Wastila Linda , Zuckerman Ilene H. , Shaffer Thomas , Blanchette Christopher M. , Stuart Bruce 
Published: September 2007

Objective. To describe the extent of drug coverage among severely mentally ill Medicare beneficiaries and to determine whether and to what extent discontinuities in prescription drug coverage influence the use of medications used to treat serious mental health conditions.Data Source. 1997–2001 Medicare Current Beneficiary Surveys.Study Design. We use a zero‐inflated negative binomial model to estimate: (1) the probability of not receiving any mental health drug and (2) the number of medications received, adjusting for age, race, income, census region, health status, and comorbidity. Severe mental illness is defined using inpatient and outpatient claims with ICD‐9 codes of schizophrenia, other psychotic disorders, bipolar disorders, and major depression. Mental health medications include antidepressants, antipsychotics, mood stabilizers, anxiolytic/sedative‐hypnotics, and stimulants. Prescription drug coverage is assessed as full coverage (0 percent discontinuities), no coverage (100 percent discontinuities), or as discontinuous coverage, measured as 1–25, 26–50, and 51–99 percent of time without coverage.Data Collection/Extraction Methods. We constructed three 3‐year longitudinal cohorts of severely mentally ill Medicare beneficiaries residing in the community (n=901).Principal Findings. Severely mentally ill Medicare beneficiaries with drug coverage discontinuities are more likely than their continuously insured peers not to receive medications used to treat mental health disorders, with the most significant impact seen in the probability of receiving any psychiatric medications. Analysis of two therapeutic classes—antidepressants and antipsychotics—revealed varying impacts of drug gaps on both probability of any drug use, as well as number of medications received among users.Conclusions. Severely mentally ill Medicare beneficiaries may be particularly vulnerable to the Medicare Part D drug benefit design and, as such, warrant close evaluation and monitoring to insure adequate access to and utilization of medications used to manage mental illness.
Development of a Measure of Physician Engagement in Addressing Racial and Ethnic Health Care Disparities
Authors: Alexander G. Caleb , Lin Shang , Sayla Maliha A. , Wynia Matthew K. 
Published: September 2007

Objective. To develop a measure of physician engagement in addressing health care disparities.Data Sources/Study Design. Cross‐sectional survey of a national sample of physicians assessing each hypothesized component of engagement (Awareness, Reflection/Empowerment, and Action [AREA]).Data Collection/Extraction Methods. Results examined using factorial analysis; predictive validity of final scale examined among highly engaged physicians.Principal Findings. A nine‐item scale derived from the AREA model has face validity, content validity, and applicability to a diverse group of physicians in measuring engagement. Partial correlations confirmed the mediating role of Reflection and/or Empowerment between Awareness and Action. Use of the scale among expert physicians suggests it reliably detects highly engaged physicians.Conclusions. A nine‐item survey can measure physician engagement in addressing health care disparities.