Diabetes education needs of family members caring for American Indian elders.

Purpose: This qualitative study investigated diabetes care management among family members of American Indian elders with self-care limitations. Focus groups were used to examine the reasons for and content of diabetes care management, the challenges faced, and the support services needed.

Methods: Five focus groups were conducted with family caregivers from six tribes.

Intuitive covariation assessment of the illusory correlation.

Most of the research concerned with the illusory correlation is modeled after the seminal work of D. L. Hamilton and R.

Pharmacological manipulation of central nitric oxide/guanylate cyclase activity alters Fos expression by rat hypothalamic vasopressinergic neurons during acute glucose deprivation.

Neurohypophyseal secretion of arginine vasopressin is stimulated by decreased systemic glucose availability. Nitric oxide is produced by paraventricular and supraoptic magnocellular neurons, and is implicated in central mechanisms controlling plasma sasopressin and glucose levels. The current studies investigated the role of this neurotransmitter in glucoprivic induction of AP-1 transcriptional activity in hypothalamic vasopressinergic neurons by examining whether pharmacological manipulation of central nitric oxide/guanylate cyclase/cGMP signaling alters nuclear accumulation of Fos immunoreactivity in these cells.

Intraventricular lactate infusion attenuates the transactivational effects of the glucose antimetabolite, 2-deoxy-D-glucose, on hypothalamic vasopressinergic neurons.

Glucopenia stimulates neurohypophyseal arginine vasopressin (AVP) secretion and expression of the transcription factor, Fos, by paraventricular (PVN) and supraoptic (SON) magnocellular neurons. Recent studies suggest that central compensatory responses to glucose substrate imbalance are initiated by regulatory signals of periventricular origin. Since the glycolytic endproduct, lactate, is a preferred substrate for central neuronal respiration, we investigated whether intracerebroventricular (i.

Beta-adrenergic-blocking agents in bronchospastic diseases: a therapeutic dilemma.

Cardioselective beta-blockers should be administered starting with a low dosage under direct medical observation. Bronchodilators should be readily available or may be coadministered. Because of several advantages, agents such as metoprolol, atenolol, and, in some cases, esmolol should be the first agents considered.

Effects of mu and kappa opioid receptor antagonists on glucoprivic induction of Fos immunoreactivity in the rat preoptic area and hypothalamus.

Interoreceptors in the central nervous system elicit compensatory behavioral and physiological responses to cellular glucopenia. Antagonism of mu and kappa opioid receptors attenuates glucoprivic hyperphagia, findings that implicate these peptidergic receptors in the central processing of metabolic regulatory signals. Several hypothalamic structures of critical importance for the regulation of energy balance exhibit one or both of these receptors.

Stability and bioequivalence studies of two marketed formulations of coenzyme Q10 in beagle dogs.

Coenzyme Q10 (CoQ10), a highly lipophilic compound present in the inner mitochondrial membrane, is essential for production of cellular energy in the form of ATP. CoQ10 is used as an antioxidant and also in the treatment of various cardiovascular disorders. The relative bioavailabilities of powder filled capsule (I) and oil-based formulation (II) of CoQ10 were compared in beagle dogs in an open, randomized, multiple dose, cross-over design.

Effect of chiral enhancers on the permeability of optically active and racemic metoprolol across hairless mouse skin.

The stratum corneum, the rate-limiting barrier in transdermal drug delivery, is chiral in nature and enantiomers behave differently with respect to their transport across the skin, resulting in enantioselective permeation. The permeation characteristics of individual enantiomers of metoprolol free base (MB) were investigated using hairless mouse skin. The influence of chiral permeation enhancers, l-menthol and (+/-)-linalool, on the permeation of MB was also investigated.

Comparative neurochemical effects of repeated methyl parathion or chlorpyrifos exposures in neonatal and adult rats.

Several studies have reported higher sensitivity based on lethality in young animals compared to adults following acute exposure to organophosphorus insecticides (OPs). We propose that age-related differences in sensitivity to OPs may differ qualitatively and quantitatively with different OPs and varying exposure conditions (e. g.

A unique paclitaxel-mediated modulation of the catalytic activity of topoisomerase IIalpha.

Paclitaxel (Taxol) is known to act by polymerizing and stabilizing microtubules. In spite of a known target, the existence of additional targets is suggested by a poor understanding of the mechanism(s) underlying eventual cell death by paclitaxel and by the drug's high efficacy, as compared to other spindle poisons. Based on the enhanced sensitivity of a mutant DNA double-strand break repair-deficient Chinese hamster ovary cell line to paclitaxel as well as to various topoisomerase (Topo) II poisons, it was hypothesized that paclitaxel, in addition to having an effect on microtubules, may also alter the activity of Topo II.

Glucosidation of betulinic acid by Cunninghamella species.

Microbial transformation of the antimelanoma agent betulinic acid (1) was studied. Preparative scale biotransformation with resting-cell suspensions of Cunninghamella species NRRL 5695 resulted in the production of a fungal metabolite of 1, which has been characterized as 28-O-beta-D-glucopyranosyl 3beta-hydroxy-lup-20(29)-en-28-oate (2) based on spectral and enzymic data. The in vitro cytotoxicity assay of metabolite 2 revealed no activity against several human melanoma cell lines.

Toxicant-inflicted injury and stimulated tissue repair are opposing toxicodynamic forces in predictive toxicology.

These studies were designed to investigate the dose response for liver injury and tissue repair induced by exposure to four structurally and mechanistically dissimilar hepatotoxicants, individually and as mixtures. The objective was to illuminate the impact of the extent and timeliness of tissue repair on the ultimate outcome of toxicity. Dose-response relationships for trichloroethylene (TCE), allyl alcohol (AA), thioacetamide (TA), and chloroform alone or as mixtures were studied.

Chemical delivery systems: evaluation of physicochemical properties and enzymatic stability of phenylephrone derivatives.

The physicochemical properties and enzymatic stability of esters of phenylephrone, synthesized on the basis of the chemical delivery system (CDS) concept, were studied as a new class of mydriatic agents. Potentiometrically determined ionization constants (pKa) of the novel compounds were in the range 7.19-7.

Organophosphorus pesticides: do they all have the same mechanism of toxicity?

Organophosphorus (OP) pesticides are used extensively to control agricultural, household and structural pests. These pesticides constitute a diverse group of chemical structures exhibiting a wide range of physicochemical properties, with their primary toxicological action arising from inhibition of the enzyme acetylcholinesterase (AChE, EC 3.1.

Growth inhibitory effect of L-canavanine against MIA PaCa-2 pancreatic cancer cells is not due to conversion to its toxic metabolite canaline.

L-Canavanine (CAV) is an arginine (ARG) analog isolated from the jack bean, Canavalia ensiformis. CAV becomes incorporated into cellular proteins of MIA PaCa-2 human pancreatic cancer cells and the aberrant, canavanyl proteins are not preferentially degraded. Hydrolytic cleavage of CAV to canaline (CAN) and urea is mediated by arginase.

2-pyridylthioureas: novel nonpeptide somatostatin agonists with SST4 selectivity.

Somatostatin [somatotropin release-inhibiting factor (SRIF)] is a cyclic tetradecapeptide that is a potent inhibitor of growth hormone (GH) secretion from the anterior pituitary. In addition to the inhibitory effects on GH-release, SRIF-14 and SRIF-28, a 28-amino acid form of SRIF extended from the N-terminal end, inhibit the release of a variety of other peptides including glucagon, insulin, and gastrin, and both peptides act as neurotransmitters and neuromodulators in the central nervous system and the periphery. SRIF exerts its potent inhibitory effects following binding to high affinity SRIF receptors (ssts) that have been identified on target tissues.

Induction of Fos immunoreactivity by acute glucose deprivation in the rat caudal brainstem: relation to NADPH diaphorase localization.

Neuronal nitric oxide (NO) synthase, a NADPH diaphorase (NADPH-d) enzyme, catalyzes formation of the free radical neurotransmitter, NO, and is distributed within several caudal brainstem structures. The following studies investigated whether these neuron populations express immunoreactivity for the inducible nuclear transcription factor, Fos, in response to acute glucose deprivation. Eight days after bilateral ovariectomy and subcutaneous implantation of silastic capsules containing 30 microg estradiol benzoate/ml, adult female rats were injected i.

Permeability characteristics of novel mydriatic agents using an in vitro cell culture model that utilizes SIRC rabbit corneal cells.

The purpose of this study was to evaluate the permeability characteristics of a previously reported in vitro corneal model that utilizes SIRC rabbbit corneal cells and to investigate the permeability of three novel esters of phenylephrone chemical delivery systems (CDS) under different pH conditions using this in vitro model. The SIRC rabbit corneal cell line was grown on transwell polycarbonate membranes, and the barrier properties were assessed by measuring transepithelial electrical resistance (TEER) using a voltohmmeter. The permeabilities of esters of phenylephrone CDS across the SIRC cell layers were measured over a pH range 4.

ATP-sensitive K(+) Channels in the Regulation of Feeding Behavior: A Hypothesis.

In this paper we present a relatively narrow view of a wide body of literature, the elements of which share two featuresin common: an effect on food intake, and a relationship to an ATP-sensitive K(+) channel. With only sparse direct evidence available, we propose and provide circumstantial evidence supporting the hypothesis that ATP-sensitive potassium channels are ubiquitously relevant molecular integrators of energy balance, playing a role in numerous neuronal and hormonal systems involved in the maintenance of both energy intake and energy expenditure. Further, we focus on a few of the latest findings in this area which suggest that out hypothesis, while seemingly tenable, may involve process with unexpected levels of complexity.

The Effect of Centrally Administered Glibenclamide, Tolbutamide and Diazoxide on Feeding in Rats.

While there are many theories on the control of feeding behavior that emphasize a role for energy substrates and their metabolism, the mechanism that couples changes in energy substrate supply and metabolism to alterations in food intake remains unclear. The purpose of the present project was to investigate the possibility that central ATP-sensitive potassium (KATP(+)) channels may serve as integrators between cellular energetics and alterations in neuronal activity that control feeding, such that pharmacologic manipulation of the channels would result in alterations in feeding behavior. Intracerebroventricular (ICV) injections of the KATP(+) channel blocker glibenclamide significantly increased feeding in fasted and fed male Sprague-Dawley rats.

Role of tissue repair in toxicologic interactions among hepatotoxic organics.

It is widely recognized that exposure to combinations or mixtures of chemicals may result in highly exaggerated toxicity even though individual chemicals might not be toxic at low doses. Chemical mixtures may also cause additive or less than additive toxicity. From the perspective of public health, highly exaggerated toxicity is of significant concern.

Temporal changes in tissue repair permit survival of diet-restricted rats from an acute lethal dose of thioacetamide.

Although, diet restriction (DR) has been shown to substantially increase longevity while reducing or delaying the onset of age-related diseases, little is known about the mechanisms underlying the beneficial effects of DR on acute toxic outcomes. An earlier study (S. K.