Use and cost of branded and generic drugs in patients with coronary heart disease--results from a prospective survey of 1008 patients in two London hospitals.

Background: Combination therapy with three classes of drug, antiplatelet, cholesterol and blood pressure lowering treatment markedly reduce the risk of recurrent cardiovascular events in patients with coronary heart disease (CHD). Within each class, generic and branded (patented) drugs are available which have similar efficacy but differ in cost.

Aims: (i) To assess the extent to which preventive medical drugs are prescribed in patients with CHD and to examine the reasons for drug omissions and (ii) to assess the relative use of branded and generic drugs and the reasons for drug selection.

Forebrain sites of NPY action on estrous behavior in Syrian hamsters.

Food deprivation and similar metabolic challenges inhibit estrous behavior in female Syrian hamsters. The relevant metabolic cues appear to be detected in the hindbrain, and this information is then relayed synaptically to the forebrain circuits controlling estrous behavior. Neuropeptide Y (NPY) may be one of the neuropeptides/neurotransmitters serving this function.

Effect of naltrexone on food intake and body weight in Syrian hamsters depends on metabolic status.

Opioids are a family of neuropeptides involved in the control of food intake and regulation of body weight. In general, nonselective opioid antagonists have inhibited food intake in a variety of paradigms in rodent species. Syrian hamsters may be an exception to the general findings.

Disinhibition of female sexual behavior by a CRH receptor antagonist in Syrian hamsters.

Several conditions that inhibit female sexual behavior are thought to be associated with altered corticotropin-releasing hormone (CRH) activity in the brain. The present experiments examined the hypothesis that endogenous CRH receptor signaling mediates the inhibition of estrous behavior by undernutrition and in other instances of sexual dysfunction. Intracerebroventricular (ICV) infusion of CRH or urocortin inhibited estrous behavior in ovariectomized steroid-primed hamsters.

Effects of naltrexone and CCK on estrous behavior and food intake in Syrian hamsters.

Food deprivation inhibits estrous behavior in several species of rodents, but little is known about the neurotransmitter systems mediating this phenomenon. We determined whether partial blockade of opioid receptors by continuous infusion of naltrexone and/or acute peripheral injection of cholecystokinin (CCK) administration would overcome the suppressive effects of food deprivation on estrous behavior in Syrian hamsters. Contrary to expectation, naltrexone produced a slight suppression of estrous behavior, and systemic CCK administration had no effect.

Feeding after fourth ventricular administration of neuropeptide Y receptor agonists in rats.

Neuropeptide Y (NPY) and peptide YY (PYY) stimulate food intake after injection into the fourth cerebral ventricle, suggesting that NPY receptors in the hindbrain are targets for the stimulatory effect of these peptides on food intake. However, the NPY/PYY receptor subtype mediating the feeding response in the hindbrain is not known. To approach to this question we compared dose-effect of several NPY receptor agonists to stimulate food intake in freely-feeding rats 60- and 120-min after injection into the fourth cerebral ventricle.

Neuropeptide Y inhibits estrous behavior and stimulates feeding via separate receptors in Syrian hamsters.

Central injections of neuropeptide Y (NPY) increase food intake in Syrian hamsters; however, the effect of NPY on sexual behavior in hamsters is not known nor are the receptor subtypes involved in feeding and sexual behaviors. We demonstrate that NPY inhibits lordosis duration in a dose-related fashion after lateral ventricular injection in ovariectomized, steroid-primed Syrian hamsters. Under the same conditions, we compared the effect of two receptor-differentiating agonists derived from peptide YY (PYY), PYY-(3-36) and [Leu(31),Pro(34)]PYY, on lordosis duration and food intake.

Intracerebroventricular glucagon-like peptide-1 (7-36) amide inhibits sham feeding in rats without eliciting satiety.

Glucagonlike peptide-1 (7-36) amide (GLP-1) and its receptors are present in several brain regions and may play a role in the physiological control of feeding. To investigate the effect of GLP-1 on eating in the absence of postingestive food stimuli, rats were implanted with gastric cannulas for sham feeding and lateral ventricular cannulas for infusion of GLP-1. Rats (n = 10) sham fed 0.

Regional localization of specific [125I]leptin binding sites in rat forebrain.

Specific [125I]leptin receptor binding sites have been identified in choroid plexus (CP), but have eluded regional localization within the brain parenchyma. To optimize specific [125I]leptin binding in brain loci, we ran experiments varying the pH of incubation buffers. We found that specific [125I]leptin binding in CP was strikingly pH dependent with the most acidic buffer, pH 5.

Intracerebroventricular angiotensin II increases intraoral intake of water in rats.

Ad lib and intraoral intake tests can separate the effects of drugs on the appetitive and consummatory phases of ingestive behavior. Central angiotensin II increases ad lib intake from water bottles, but its effect on intraoral intake has not been examined. Rats with both lateral intracerebroventricular (i.

The effect of centrally administered CCK-receptor antagonists on food intake in rats.

Cholecystokinin (CCK) receptors are classified as two subtypes, designated CCK(A) and CCK(B), and both subtypes are found in brain and peripheral tissues of rats. CCK-8 has been shown to act peripherally to reduce meal size, and this satiating action can be blocked by CCK(A)-receptor antagonists. Recent evidence suggests that, in addition to the peripheral action of CCK, central CCK mechanisms may also be involved in satiety.

A transgenic mouse model to study transsynaptic regulation of tyrosine hydroxylase gene expression.

Previous studies demonstrated that 9 kb of the rat tyrosine hydroxylase (TH) 5' flanking sequence directed appropriate spatiotemporal expression of a lacZ reporter gene to catecholaminergic cells in the CNS of transgenic mice. In the present study, specificity of transgene expression was further extended to demonstrate cell type-specific functional regulation of lacZ expression using manipulations known to alter endogenous TH expression. Alterations in lacZ reporter expression should parallel changes in endogenous TH levels if the DNA elements mediating these functional changes of TH expression in vivo reside within the 9 kb of the TH promoter region.

The increased satiating potency of CCK-8 by estradiol is not mediated by upregulation of NTS CCK receptors.

Estradiol benzoate (EB) increases the satiating effect of CCK-8 in ovariectomized rats. It is possible that this effect of EB is due to upregulation of CCKA receptors in the terminals of vagal afferent fibers because these receptors have been implicated in the mediation of the satiating effect of intraperitoneally injected CCK-8. To test this hypothesis, we used in vitro quantitative autoradiography to measure the effects of EB on the binding characteristics of CCK receptors in the nucleus tractus solitarius (NTS), a region that contains central terminal projections of abdominal vagal afferent fibers.

Lack of NPY-induced feeding in cobalt protoporphyrin-treated rats is a postreceptor defect.

The administration of cobalt protoporphyrin results in transient decreases in food intake and prolonged weight loss in rats. After IVC injection of cobalt protoporphyrin, the food intake of treated rats falls to 10% of vehicle-treated control rats within 48 h. At the same time, the concentrations of mRNA for neuropeptide Y increase approximately twofold in the hypothalamus.

Characterization of type A and type B CCK receptor binding sites in rat vagus nerve.

We employed quantitative receptor autoradiography to analyze pharmacological properties of 125I-Bolton Hunter cholecystokinin (CCK-8)-labeled binding sites in sections of rat cervical vagus nerve that had been ligated 24 h prior to extraction. Binding densities were detected in segments of nerve proximal and distal to the ligature. Analysis was confined to proximal segments.

Decreased behavioral effects of daily intracerebroventricular bombesin.

Intracerebroventricular (ICV) bombesin increases grooming and decreases food intake in rats. We examined tolerance to these effects by administering a daily injection of either saline or 25 ng bombesin to rats for 8 days via lateral ventricular cannulas. Food intake and grooming were monitored.

Trypsin inhibitor and maternal reunion increase plasma cholecystokinin in neonatal rats.

Intragastric soybean trypsin inhibitor increased plasma CCK bioactivity by 87% in nondeprived, 9-12-day-old rat pups. Reunion with the dam for 1 h after overnight maternal deprivation also increased plasma CCK significantly. These results demonstrate that CCK can be released from the small intestine of rats as early as postnatal day 9.

Characterization of axonally transported [125I]PYY binding sites in rat vagus nerve.

Quantitative receptor autoradiography was used to characterize [125I]PYY binding to slide-mounted sections of rat cervical vagus nerve which had been ligated 24 h prior to extraction. Saturation and competitive binding characteristics were determined for the accumulation of binding sites detected in the segment of the nerve proximal to the ligature. High and low affinity binding components were resolved (Kd = 93 pM and 2.

Evidence for separate receptors for insulin and insulin-like growth factor-I in choroid plexus of rat brain by quantitative autoradiography.

Binding of insulin and insulin-like growth factor-I (IGF-I) to the choroid plexus was quantitatively characterized using autoradiography and computer densitometry. Slide-mounted brain slices were incubated in 0.1 nM [125I]-insulin or [125I]-[Thr59]IGF-I.

Effect of fourth ventricular neuropeptide Y and peptide YY on ingestive and other behaviors.

We studied the effect of fourth intracerebroventricular administration of neuropeptide Y (NPY) and peptide YY (PYY) on ingestive and other behaviors in awake nondeprived rats. Injection of NPY or PYY into the fourth ventricle produced a significant dose-related increase in food intake and reduction in the latency to eat. PYY was more potent than NPY in increasing food intake and decreasing latency to eat, suggesting that PYY-preferring receptors sensitive to the orexigenic effects of NPY and PYY exist in the hindbrain.

Insulin binding in the hypothalamus of lean and genetically obese Zucker rats.

Recent reports have suggested that the obesity and hyperphagia of the genetically obese Zucker rat may be related to defective insulin action or binding in the hypothalamus. We used quantitative autoradiography to determine if insulin binding is altered in specific hypothalamic nuclei associated with food intake. Insulin binding was measured in the arcuate (ARC), dorsomedial (DMN), and ventromedial (VMN) hypothalamic nuclei of 3-4-month-old lean (Fa/Fa) and genetically obese (fa/fa) Zucker rats.

Characterization of insulin-like growth factor I receptors in the median eminence of the brain and their modulation by food restriction.

High affinity binding sites for 125I-labeled [Thr59]insulin-like growth factor I (IGF-I) were measured in rat median eminence by in vitro autoradiography with slide-mounted sections of frozen rat brain. Specific binding of 0.1 nM iodo-[Thr59]IGF-I to brain slices reached maximum by 12 h at 4 C and was unchanged at 24 h.

Localization of binding sites for insulin-like growth factor-I (IGF-I) in the rat brain by quantitative autoradiography.

In vitro quantitative autoradiography was used to localize IGF-I binding sites in rat brain. Slide-mounted sections of frozen rat brain were incubated in 0.01 nM 125I[Thr59]IGF-I, alone or mixed with 10 nM unlabeled [Thr59]IGF-I or insulin, for 22 h at 4 degrees C and apposed to LKB Ultrofilm.

Localization of 125I-insulin binding sites in the rat hypothalamus by quantitative autoradiography.

In vitro autoradiography and computer video densitometry were used to localize and quantify binding of 125I-insulin in the hypothalamus of the rat brain. Highest specific binding was found in the arcuate, dorsomedial, suprachiasmatic, paraventricular and periventricular regions. Significantly lower binding was present in the ventromedial nucleus and median eminence.

Identification of binding sites for an insulin-like growth factor (IGF-I) in the median eminence of the rat brain by quantitative autoradiography.

The microanatomical location of IGF-I binding in the rat brain was determined by in vitro autoradiography with slide-mounted sections of frozen brain. Sections incubated in 0.1 nM [125I]-iodo-IGF-I produced a dense grain concentration in regions of the autoradiographic image corresponding to the external palisade zone of the median eminence; other hypothalamic regions were not so heavily labeled.