Dosage choices of rats for morphine, for heroin, and between morphine and heroin.

Each of four doses of intravenous morphine and four of intravenous heroin was tested for reinforcing efficacy, and comparisons were made among the four morphine doses, among the four heroin doses, and between morphine and heroin. Rats with venous catheters performed one daily forced run for 75 s to one of the two compartments of a spatial choice apparatus, with compartments and doses or drugs alternating over days. In each trial, the accessible compartment depended on which dose (including zero dose) or drug a rat was to receive.

Factors predicting survival, changes in activity limitations, and disability in a geriatric post-stroke population.

This study is based on data for individuals with a history of stroke taken from the NIA-sponsored Longitudinal Study of Aging (LSOA), 1984-1990. It provides information on the factors predicting survival and changes in disability and activity limitations in this cohort with stroke or cerebrovascular accident over the period of two years, 1984 to 1986. The results indicate that individuals who were less than 80 years old had higher chances of survival and were likely to show reduced activity limitations and disabilities.

Antimitotic intervention with colchicine alters the outcome of o-DCB-induced hepatotoxicity in Fischer 344 rats.

Although, hepatotoxic injury of 1,2-dichlorobenzene (o-DCB) is greater in Fischer 344 (F344) as compared to Sprague-Dawley (S-D) rats, this interstrain difference does not transcend into any difference in lethal effects of o-DCB. Interstrain difference in compensatory tissue repair has been suggested as the underlying mechanism for the lack of strain differences in lethality (S.G.

Reversal of doxorubicin resistance in multidrug resistant melanoma cells in vitro and in vivo by dipyridamole.

The occurrence of multidrug resistance (MDR) decreases the clinical utility of several anticancer agents, including doxorubicin (DOX). A transmembrane efflux pump, P-glycoprotein (P-gp), is frequently implicated in the development of MDR in tumor cells. Dipyridamole (DP), a clinically used antiplatelet drug, enhances the cytotoxicity of the anticancer drugs affected by MDR.

Potentiation of organophosphorus-induced delayed neurotoxicity following phenyl saligenin phosphate exposures in 2-, 5-, and 8-week-old chickens.

Phenylmethylsulfonyl fluoride (PMSF), a nonneuropathic inhibitor of neurotoxic esterase (NTE), is a known potentiator of organophosphorus-induced delayed neurotoxicity (OPIDN). The ability of PMSF posttreatment (90 mg/kg, sc, 4 hr after the last PSP injection) to modify development of delayed neurotoxicity was examined in 2-, 5-, and 8-week-old White Leghorn chickens treated either one, two, or three times (doses separated by 24 hr) with the neuropathic OP compound phenyl saligenin phosphate (PSP, 5 mg/kg, sc). NTE activity was measured in the cervical spinal cord 4 hr after the last PSP treatment.

Tissue injury and repair as parallel and opposing responses to CCl4 hepatotoxicity: a novel dose-response.

Recent studies indicate that the rate and extent of tissue repair, elicited as an endogenous response to toxic insult, are critical determinants in the ultimate outcome of hepatic injury. Therefore, the objective of this study was to develop a dose-response relationship for CCl4 measuring liver injury and tissue repair as two simultaneous but opposing responses. Male Sprague-Dawley rats were injected with a 40-fold dose range of CCl4 (0.

Comparative evaluation of the severity of gastric ulceration by solid dispersions and coprecipitates of indomethacin.

The ulcerogenic activity of indomethacin was studied in rats following single and chronic doses of indomethacin in the form of pure drug, solid dispersions and coprecipitates. Each formulation was administrated as a suspension in a 2% methylcellulose solution. Gastrointestinal ulceration was assessed, four hours after a single dose and 24 hours following the last dose of a chronic four day dosing regimen, by counting the number of lesions and ulcers present.

Effects of chlorpyrifos on high-affinity choline uptake and [3H]hemicholinium-3 binding in rat brain.

High, subcutaneous doses of the organophosphorus insecticide chlorpyrifos (CPF) in adult male rats can be well-tolerated despite extensive and persistent acetylcholinesterase (AChE) inhibition. We propose that changes in acetylcholine synthesis could modulate the toxicity associated with extensive AChE inhibition following CPF exposure. High-affinity choline uptake (HACU, the rate-limiting step in acetlcholine synthesis) and binding to [3H]-hemicholinium-3 (HC-3, a specific ligand for the choline transporter) were chosen as indicators of acetylcholine synthesis.

Effect of permeation enhancers on the release of ketoprofen through transdermal drug delivery systems.

Feasibility studies were performed to prepare membrane controlled transdermal drug delivery system of ketoprofen containing Carbopol 934p gels. The ability of permeation enhancers such as oleic acid, polyethylene glycol 400 and propylene glycol to provide improved performance has been investigated. The variables studied were drug loading, type of the permeation enhancers, and their concentration.

Stimulated tissue repair prevents lethality in isopropanol-induced potentiation of carbon tetrachloride hepatotoxicity.

Published reports on the alcohol potentiation of CCl4 toxicity indicate that in spite of enhanced hepatotoxicity there is no increase in lethality. The objective of this study was to investigate the mechanism involved in animal survival despite significantly enhanced liver injury. Male Sprague-Dawley rats (175-225 g) were treated with isopropanol (ISOP, 2.

Efficient tissue repair underlies the resiliency of postnatally developing rats to chlordecone + CCl4 hepatotoxicity.

It is often assumed that at a younger age populations are at higher risk of toxic effects from exposure to toxic chemicals. Recent studies have demonstrated that neonate and postnatally developing rats are resilient to a wide variety of structurally and mechanistically dissimilar hepatotoxicants such as galactosamine, acetaminophen, allyl alcohol, and CCl4. Most interestingly, young rats survive exposure to the lethal combination of chlordecone (CD) + CCl4 known to cause 100% mortality in adult male and female rats.

Role of nutrition in the survival after hepatotoxic injury.

Nutritional status is an important factor in determining susceptibility to toxic chemicals. While macro and micronutrients may affect many aspects of Stage I and Stage II of toxicity, in this paper, the influence of macronutrients as sources of energy required for cell division and tissue repair mechanisms on the outcome of hepatic injury is discussed. Male Sprague-Dawley rats maintained on normal rodent chow and 15% glucose (as a source of energy for the centrilobular hepatocytes) in drinking water for 7 days experienced an increased lethality from structurally and mechanistically different centrilobular hepatotoxicants (acetaminophen, thioacetamide, chloroform and carbon tetrachloride), while male Sprague-Dawley (S-D) rats fed rat chow containing palmitic acid (PA, 8% w/w, as a source of energy for the periportal hepatocytes) and L-carnitine (LC, 2 mg/ml, as a mitochondrial carrier for the supplemented fatty acids) in drinking water for 7 days were protected from a LD100 dose (600 mg/kg, i.

Effect of an antimitotic agent colchicine on thioacetamide hepatotoxicity.

In an earlier study we established that timely and adequate tissue repair response following the administration of a six-fold dose-range of thioacetamide (TA; 50, 150, and 300 mg/kg) prevented progression of injury and led to recovery and animal survival. Delayed and attenuated repair response after the 600 mg/kg TA dose resulted in a marked progression of injury and 100% lethality. The objective of the present study was to further scrutinize this concept in an experimental protocol in which we hypothesized that a selective ablation of the tissue repair response should lead to lethality from the nonlethal, moderately toxic doses of 150 and 300 mg/kg TA.

Neurochemical and neurobehavioral effects of repeated gestational exposure to chlorpyrifos in maternal and developing rats.

Acute exposure to the organophosphate pesticide chlorpyrifos (CPF) on gestation day 12 (GD12, 200 mg/kg/ml, SC) causes extensive neurochemical changes in maternal brain but lesser changes in fetal brain. In the present study, we examined the relative neurotoxicity of repeated, lower-level CPF exposures during gestation in rats. Pregnant Sprague-Dawley rats were exposed to CPF (6.

Nutritional modulation of the final outcome of hepatotoxic injury by energy substrates: an hypothesis for the mechanism.

Survival after hepatocellular injury and necrosis may depend on the ability of the remaining hepatocytes to divide and restore an adequate population of functioning cells. Although adequate nutritional support is necessary for liver regeneration after severe liver damage, much is yet to be discovered concerning which nutritional factors are critical for liver regeneration. Clinically, nutritional substances are administered only from the energy aspect, without regard to whether or how these substrates may facilitate or impede liver tissue repair processes.

Strain differences in tissue repair response to 1,2-dichlorobenzene.

Fischer 344 (F344) rats are reportedly 75-fold more sensitive than Sprague Dawley (S-D) rats to 1,2-dichlorobenzene (o-DCB) hepatotoxicity. Lethality studies were conducted since no information was available regarding the ultimate consequence of this sensitivity in terms of animal survival in the two strains. LD50S for o-DCB (1.

Inappropriate drug prescribing and related outcomes for elderly medicaid beneficiaries residing in nursing homes.

Problems of drug prescribing are related to poor economic and clinical outcomes, and there is a common perspective that prescribing in nursing homes is suboptimal. This study purported to determine how prescribing of "inappropriate" drugs, health care provider-related factors, and patient demographics were related to the cost of pharmaceutical services and the mortality of elderly Medicaid beneficiaries in Louisiana's Intermediate Care Facilities I during 1994. Inappropriate drugs for this retrospective, observational, and cross-sectional study were identified using explicit criteria.

Permeability of a soft steroid, loteprednol etabonate, through an excised rabbit cornea.

The objective of this work was to study the in vitro permeability characteristics of a "soft" steroid, loteprednol etabonate 1 in different vehicles across excised rabbit cornea using a transcorneal permeation system. The vehicles studies were aqueous solutions of beta-cyclodextrin derivatives; 2-hydroxypropyl beta-cyclodextrin (HPCD) and heptakis (2,6-di-O-methyl) beta-cyclodextrin (DMCD); and DMCD together with 5 and 10% propylene glycol (PG) or dimethyl sulfoxide (DMSO). Two experimental suspension products of the steroid, 0.