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At least 937 records · Page 52Linked to original sources
PubMed1998

Bioavailability, multiple-dose pharmacokinetics, and biotransformation of the aldose reductase inhibitor zopolrestat in dogs.

Zopolrestat (Alond) is a new drug that is being evaluated as an aldose reductase inhibitor for the treatment of diabetic complications. The bioavailability in dogs of a 2 mg/kg oral dose of zopolrestat was 97.2%. In a 1-year, multiple-dose, pharmacokinetic study, systemic exposure increased with increasing dose (50, 100, and 200 mg/kg/day), and there were no consistent changes in exposure with multiple dosing. Renal clearance at 1 year appeared to be higher in males. The magnitude of the potential gender difference in exposure was relatively small and was unlikely to have had a meaningful impact on the pharmacokinetics of zopolrestat in dogs. In studies with bile duct-cannulated dogs, radioactivity from [14C]zopolrestat was primarily eliminated as unchanged drug and acyl glucuronide in the bile and feces (77.3% of the dose) and in urine (18.3% of the dose). The concentrations of acyl glucuronide in urine and feces were approximately 50% of the zopolrestat concentrations. Minor metabolites (each accounting for <1% of the dose) included those resulting from hydroxylation of the phthalazinone ring and glutathione conjugation of the benzothiazole ring.

Administration, Oral↗
PubMed2003

Is there a causal relationship between exposure to diesel exhaust and multiple myeloma?

This article presents a comprehensive critical review of the epidemiology of multiple myeloma in relation to occupational diesel exhaust exposure. The review includes cohort and proportional mortality studies of workers exposed to diesel exhaust, and population-based case-control studies of multiple myeloma. None of the cohort or proportional mortality studies reported a significant increase of multiple myeloma in relation to diesel exhaust, with the exception of a study of Danish truck drivers. Several limitations in this Danish study (such as inadequate cohort identification, small number of multiple myeloma deaths and inappropriate analytical method) made the result unreliable. Furthermore, the data in this study of Danish truck drivers were part of and, hence, superseded by a large study in Denmark, which did not find any increased risk of multiple myeloma. Similarly, none of the case-control studies reported a significant increase of multiple myeloma in relation to diesel exhaust, with the exception of the smallest case-control study based on multiple myeloma patients in central and southeast Sweden. The result of this small Swedish study was not reliable because of incomplete case ascertainment, inappropriate controls and confounding. Furthermore, the data in this small Swedish study were part of and, hence, superseded by a large national study of workers exposed to diesel exhaust in Sweden, which did not find any increased risk of multiple myeloma. Other than the study of Danish truck drivers and the small case-control study of multiple myeloma patients in central and southeast Sweden, all other epidemiological investigations consistently reported no increase of multiple myeloma in relation to occupational diesel exhaust exposure. Furthermore, none of the studies reported a positive exposure-response relationship between diesel exhaust and multiple myeloma. Several studies that analysed data by jobs or occupations according to level of exposure and by duration of exposure did not find any upward trend. In addition to the review, a formal causation analysis based on an application of the Hill criteria confirms that there is no causal relationship between diesel exhaust and multiple myeloma.

Denmark↗
PubMedDate not supplied

A feasibility study of cumulative risk assessment methods for drinking water disinfection by-product mixtures.

Humans are exposed daily to complex mixtures of chemicals, including drinking water disinfection by-products (DBPs) via oral, dermal, and inhalation routes. Some positive epidemiological and toxicological studies suggest reproductive and developmental effects and cancer are associated with consumption of chlorinated drinking water. Thus, the U.S. Environmental Protection Agency (EPA) conducted research to examine the feasibility of evaluating simultaneous exposures to multiple DBPs via all three exposure routes. A cumulative risk assessment approach was developed for DBP mixtures by combining exposure modeling and physiologically based pharmacokinetic modeling results with a new mixtures risk assessment method, the cumulative relative potency factors (CRPF) approach. Internal doses were estimated for an adult female and an adult male, each of reproductive age, and for a child (age 6 yr) inclusive of oral, dermal, and inhalation exposures. Estimates of the daily internal doses were made for 13 major DBPs, accounting for activity patterns that affect the amount of human contact time with drinking water (e.g., tap water consumed, time spent showering), building characteristics (e.g., household air volumes), and physicochemical properties of the DBPs (e.g., inhalation rates, skin permeability rates, blood: air partition coefficients). A novel cumulative risk assessment method, the CRPF approach, is advanced that integrates the principles of dose addition and response addition to produce multiple-route, chemical mixture risk estimates using total absorbed doses. Research needs to improve this approach are presented.

Chlorine Compounds↗
PubMed1987

Coaxial laser energy delivery using a steerable catheter in canine coronary arteries.

Intracoronary delivery of argon laser energy was studied in eight anesthetized mongrel dogs. A No. 4.5 French single lumen catheter, with steerable guidewire and an optical fiber, was introduced through a Judkins-type femoral-coronary guiding catheter into three left anterior descending and eight left circumflex coronary arteries. A total of 65 laser energy exposures were made coaxially at 24 sites in the 11 arteries. At five sites, angiographically evident arterial perforation occurred with the first laser exposure, while at seven sites multiple laser exposures were made without angiographically evident perforation. All eight dogs remained hemodynamically stable, and were electively killed 5 +/- 1 hours following the procedure. Sections of myocardium from territories supplied by treated arteries demonstrated minimal or no pathology in 10 cases, while one territory had a small zone of early myocardial necrosis. This study suggests that standard coronary artery catheterization techniques can be used to introduce and position a steerable guidewire and an optical fiber in canine coronary arteries. Laser energy can repeatedly be delivered coaxially. Short-term deleterious effects may be reduced or eliminated, and exposure of blood elements to argon laser energy does not appear to create debris.

Animals↗
PubMedDate not supplied

Cortical cell plasma membrane alterations after in vitro alcohol exposure: prevention by GM1 ganglioside.

Using choleratoxin/antitoxin immunohistochemistry, this study examined the effects of in vitro alcohol exposure on the morphology of cell plasma membranes in mixed fetal rat cortical cultures, and assessed the neuroprotective effects of exogenous monosialoganglioside (GM1). Gangliosides are involved in critical biological functions, including maintenance of membrane integrity. Plasma membranes are directly affected by alcohol exposure through multiple mechanisms. Results indicate that exposure to alcohol altered plasma membrane morphology as assessed by staining for the surface distribution of membrane GM1. Pretreatment with endogenous GM1 ameliorated the alcohol-induced alterations.

Animals↗
PubMed1997

Varicella vaccination for healthcare workers at a university hospital: an analysis of costs and benefits.

OBJECTIVE: To demonstrate the costs and benefits of vaccinating varicella-susceptible healthcare workers at a university hospital with live, attenuated varicella-zoster virus vaccine. DESIGN: Retrospective review of employee medical records and data on the cost of special paid absence for susceptible healthcare workers after exposure to varicella or herpes zoster. SETTING: A 988-bed tertiary-care university hospital. RESULTS: In 1994, 224 hospital employees (3.4%) were susceptible to the varicella-zoster virus. There were 40 exposures to varicella and herpes zoster in that year, involving 29 of the susceptible employees. Nine (31%) of the exposed susceptibles became varicella immune by indirect fluorescent antibody testing subsequent to exposure. Seventeen (59%) have had multiple varicella exposures and special paid absences while employed by the hospital. In 1994, wages paid to healthcare workers while furloughed for the communicable period following varicella exposure totaled $38,463.93. An additional $24,748.74 was paid to replacement workers during that same time. Varicella vaccine to immunize all 224 susceptibles in 1994 would have cost $17,920. Absences due to varicella and herpes zoster exposure also result in disruptions to patient care. CONCLUSIONS: Varicella vaccination for varicella-susceptible healthcare workers at a university hospital would result in financial savings and improved patient care. We recommend that other institutions consider the costs and benefits of adopting a varicella immunization program for their susceptible employees.

Chickenpox↗
PubMed1999

Dermal application of JP-8 jet fuel induces immune suppression.

Chronic exposure to JP-8 jet fuel induces lung toxicity, adverse neurological effects and some liver and kidney dysfunction. In addition, inhalation of JP-8 induces immune suppression. Besides the lung, the other major route of JP-8 exposure is via the skin. In this study we tested the hypothesis that dermal exposure to JP-8 is immune suppressive. JP-8 was applied to the skin of adult female C3H/HeN mice and various immune parameters were examined. Dermal exposure to JP-8, either multiple small exposures (50 microl for 5 days) or a single large dose (250-300 microl) resulted in immune suppression. The induction of contact hypersensitivity was impaired in a dose-dependent manner regardless of whether the contact allergen was applied directly to the JP-8-treated skin or at a distant un-treated site. In addition, the generation of a classic delayed-type hypersensitivity reaction to a bacterial antigen (Borellia burgdorferi) injected into the subcutaneous space was suppressed by dermal application of JP-8 at a distant site. The ability of splenic T lymphocytes from JP-8-treated mice to proliferate in response to plate-bound monoclonal anti-CD3 was also significantly suppressed. Interleukin-10, a cytokine with potent immune suppressive activity, was found in the serum of JP-8-treated mice, suggesting that the mechanism of systemic immune suppression may involve the upregulation of cytokine release by JP-8. These findings confirm the immunosuppressive effects of JP-8 and demonstrate that dermal exposure to JP-8 is immunotoxic.

Administration, Cutaneous↗
PubMed2001

The utility of Poison Control Center data for assessing toxic occupational exposures among young workers.

This study assessed the utility of Poison Control Center data for identifying and describing occupational toxic exposures to youth and the associated health outcomes of such exposures. The authors reviewed 1997 data from the American Association of Poison Control Centers' Toxic Exposure Surveillance System for occupational exposures to persons 6 to 19 years old. In 1997, there were 3442 reported occupational exposure cases among 6- to 19-year-olds. Exposure cases included underage workers, exposure to multiple substances, continuous or repeated exposure to the offending substance, and exposures occurring in the home. Poison Control Centers provide unique and valuable information on toxic workplace exposures to youth. Child labor laws may be violated in many cases, and risks exist with respect to industrial work done in the home. Prospective studies with immediate follow-back are needed.

Adolescent↗
PubMed1978

The urinary melanogen cysteinyldopa in melanoma and in suntanning: Australian experience.

Determination of urine cysteinyldopa excretion is the most sensitive chemical test for the detection of melanoma metastases and has been successfully applied during the Scandinavian winter, when sun irradiation is low. The value of this determination, under Australian conditions of greater sun irradiation, has been assessed by comparing the cysteinyldopa excretion of patients with that of normal subjects exposed to sunlight. Cysteinyldopa is an intermediate in the biosynthesis of the red-brown phaeomelanin. Of 20 patients without known secondary melanoma, the cysteinyldopa concentration of "spot" urines ranged from 0 to 190 (mean 48) microgram/ml; of six known to have local metastases, 0 to 80 (mean 19) microgram/ml; and of four known to have extensive metastases 80 to 1350 (mean 330) microgram/ml. The effect of sun irradiation alone was assessed in nine healthy subjects followed one to 11 weeks before and after recorded periods of sun exposure. The cysteinyldopa concentrations of 24-hour urines ranged from 40 to 3100 microgram/ml. Increases occurred three to 10 days following sun exposure and were greatest following multiple small exposures in an individual with "Celtic" complexion. It is concluded that measurement of cysteinyldopa concentration would be of value in the follow-up of melanoma patients in Australia only if patients could be persuaded to live under conditions free of all direct sun-irradiation.

Adolescent↗
PubMedDate not supplied

Factors influencing estimation of pesticide-related wildlife mortality.

Free-ranging wildlife is regularly exposed to pesticides and can serve as a sentinel for human and environmental health. Therefore a comprehensive pesticide hazard assessment must incorporate the effects of actual applications on free-ranging wildlife. Mortality is the most readily reported wildlife effect, and the significance of these data can be realized only when placed in context with the factors that affect the gathering of this type of information. This paper reviews the variables that affect the collection of wildlife mortality data. Data show that most effects on wildlife are not observed, and much of observed mortality is not reported. Delays in reporting or in the response to a report and exposure to multiple stressors distort the exposure-effect relationship and can result in uncertainty in determining the cause of death. The synthesis of information strongly indicates that the actual number of affected animals exceeds the number recovered.

Animals↗
PubMed1996

[Evaluation of the irritative action of formaldehyde and glutaraldehyde aldehyde].

The irritative effect of formaldehyde and glutaraldehyde on the rabbit skin was determined under conditions of a single, closed exposure and under conditions of multiple, open exposure. It was revealed that the irritative effect was dependent on the concentration used, application mode and exposure duration. Under conditions of a single, 4 and 24-hour, closed exposure, threshold concentration which was inducing only slight inflammatory reaction of skin was equal to 2% of aqueous solution for both formaldehyde and glutaraldehyde. Under conditions of a 10 open exposure, threshold concentration of irritative effect on the skin was determined as 5% aqueous solution for formaldehyde and 2.5% aqueous solution for glutaraldehyde. A single administration of 0.5% aqueous solution of formaldehyde and of 0.2% aqueous solution of glutaraldehyde into the rabbit's eye induced a slight and short lasting inflammatory reaction. These concentrations were recognised as threshold ones.

Animals↗
PubMed1996

Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposure.

Some individuals remain uninfected with human immunodeficiency virus type-1 (HIV-1) despite multiple high-risk sexual exposures. We studied a cohort of 25 subjects with histories of multiple high-risk sexual exposures to HIV-1 and found that their CD8+ lymphocytes had greater anti-HIV-1 activity than did CD8+ lymphocytes from nonexposed controls. Further studies indicated that their purified CD4+ lymphocytes were less susceptible to infection with multiple primary isolates of HIV-1 than were CD4+ lymphocytes from the nonexposed controls. This relative resistance to HIV-1 infection did not extend to T-cell line-adapted strains, was restricted by the envelope glycoprotein, was not explained by the cell surface density of CD4 molecules, but was associated with the activity of the C-C chemokines RANTES, MIP-1alpha, and MIP-1beta. This relative resistance of CD4+ lymphocytes may contribute to protection from HIV-1 in multiply exposed persons.

CD4-Positive T-Lymphocytes↗
PubMed2000

Assessing exposure to violence using multiple informants: application of hierarchical linear model.

The present study assesses the effects of demographic risk factors on children's exposure to violence (ETV) and how these effects vary by informants. Data on exposure to violence of 9-, 12-, and 15-year-olds were collected from both child participants (N = 1880) and parents (N = 1776), as part of the assessment of the Project on Human Development in Chicago Neighborhoods (PHDCN). A two-level hierarchical linear model (HLM) with multivariate outcomes was employed to analyze information obtained from these two different groups of informants. The findings indicate that parents generally report less ETV than do their children and that associations of age, gender, and parent education with ETV are stronger in the self-reports than in the parent reports. The findings support a multivariate approach when information obtained from different sources is being integrated. The application of HLM allows an assessment of interactions between risk factors and informants and uses all available data, including data from one informant when data from the other informant is missing.

Adolescent↗
PubMed2005

[Chronic fatigue syndrome and multiple chemical hypersensitivity after insecticide exposure].

BACKGROUND AND OBJECTIVE: Chronic Fatigue Syndrome (CFS) and Multiple Chemical Sensitivity (MCS) are well-defined illnesses that may appear after some toxic exposures. PATIENTS AND METHOD: We report a consecutive series of 26 patients who developed CFS after exposure to insecticide products. It was associated with MCS in a third of cases. RESULTS: Toxic exposure was of labour origin after returning to usual work place after a process of fumigation. In 42% of cases there was no fulfilment of fumigation safety rules. The majority of patients were mean-aged women who developed an acute upper airway inflammatory syndrome, without muscarinic or nicotinic manifestations, followed by digestive syndrome, neurocognitive, fibromyalgic and chronic fatigue manifestations. The course of disease was shorter than 1 year in 5 cases (19%), longer than 1 year in 15(58%), and disabling in 6 cases (23%). CONCLUSIONS: Due to the possible prevention of this toxic exposure, it is very important to carefully follow measures of environment isolation and ventilation after insecticide use in order to avoid the development of these diseases.

Adolescent↗
PubMed2006

Combined effect of multiple carcinogens and synergy index.

Tumorigenesis often involves exposure to multiple carcinogens. We here construct a two-stage model, which consists of individuals in three states:normal, intermediate, and malignant. We considered a population exposed to two carcinogens and examined two exposure scenarios: (1) two carcinogens exposed separately; and (2) carcinogens are exposed simultaneously. We calculate the incidence rate of the malignant state, introducing a "synergy index" to quantify the interaction between the two carcinogens. We confirmed the results of previous analyses, but we also calculate more general situation in which each carcinogen affects both steps.

Carcinogens↗
PubMed1975

A syndrome of multiple congenital anomalies associated with teratogenic exposure.

A study of 19 patients with multiple congenital anomalies described by the acronym VACTERL (Vertebral, Anal, Cardiac, Tracheoesophageal, Renal, and Limb) revealed exposure at the vulnerable period of embryogenesis to a progestogen/estrogen compound or a progestogen alone in 13 patients. These hormones were taken as a "pregnancy test," and for a variety of other reasons. Comparison of VACTERL patients with paired and matched controls, one group with chromosomal anomalies (other than Down syndrome) and another group with functional murmurs, revealed a significant difference with respect to exposure to hormonal contraceptives. The multiple anomalies of skeletal, cardiovascular, and gastrointestinal structures recapitulate the systems involved in the thalidomide syndrome, but present a variation of the pattern. Until more definitive data are available it would be prudent to emphasize the need to verify the absence of pregnancy before initiation of oral contraception and to discontinue hormonal agents as tests for pregnancy.

Abnormalities, Drug-Induced↗
PubMed2006

Sticks, stones, and hurtful words: relative effects of various forms of childhood maltreatment.

OBJECTIVE: Childhood maltreatment is an important psychiatric risk factor. Research has focused primarily on the effects of physical abuse, sexual abuse, or witnessing domestic violence. Parental verbal aggression has received little attention as a specific form of abuse. This study was designed to delineate the impact of parental verbal aggression, witnessing domestic violence, physical abuse, and sexual abuse, by themselves and in combination, on psychiatric symptoms. METHOD: Symptoms and exposure ratings were collected from 554 subjects 18-22 years of age (68% female) who responded to advertisements. The Verbal Abuse Questionnaire was used to assess exposure to parental verbal aggression. Outcome measures included dissociation and symptoms of "limbic irritability," depression, anxiety, and anger-hostility. Comparisons were made by using effect sizes. RESULTS: Verbal aggression was associated with moderate to large effects, comparable to those associated with witnessing domestic violence or nonfamilial sexual abuse and larger than those associated with familial physical abuse. Exposure to multiple forms of maltreatment had an effect size that was often greater than the component sum. Combined exposure to verbal abuse and witnessing domestic violence had a greater negative effect on some measures than exposure to familial sexual abuse. CONCLUSIONS: Parental verbal aggression was a potent form of maltreatment. Exposure to multiple forms of abuse was associated with very large effect sizes. Most maltreated children had been exposed to multiple types of abuse, and the number of different types is a critically important factor.

Adolescent↗