Environmental modulation of D-fructose insulinotropic action

This study assessed the frequency of obtaining advance directives from patients of internal medicine residents in two Baltimore teaching programs. A survey was conducted of the medical records of 130 patients in the medical clinics from these programs. Independent variables included age, sex, and race. Dependent variables included documentation of terminal illnesses, resuscitation or code status, and discussion regarding resuscitation status. Only 25 of 130 patients (19%) had a resuscitation status recorded, 24 were documented as full resuscitation and 1 as do not resuscitate. Of subjects older than 65 years, 23% had a resuscitation status. Although 4 of 37 subjects older than 65 years had a terminal illness, none had advance directives.     

Enhanced glucose-dependent insulinotropic polypeptide secretion and insulinotropic action in glucagon-like peptide 1 receptor -/- mice

Incretins are gastrointestinal hormones that act on the pancreas to potentiate glucose-stimulated insulin secretion. Despite the physiological importance of the enteroinsular axis, disruption of glucagon-like peptide (GLP)-1 action is associated with only modest glucose intolerance in GLP-1 receptor -/- (GLP-1R -/-) mice. We show here that GLP-1R -/- mice exhibit compensatory changes in the enteroinsular axis via increased glucose-dependent insulinotropic polypeptide (GIP) secretion and enhanced GIP action. Serum GIP levels in GLP-1R -/- mice were significantly elevated versus those in +/+ control mice after an oral glucose tolerance test (369 +/- 40 vs. 236 +/- 28 pmol/l; P < or = 0.02). Furthermore, GIP perfusion of mice pancreas and isolated islets in the presence of elevated glucose concentrations elicited a significantly greater insulin response in GLP-1R -/- than in +/+ mice (P < or = 0.02-0.05). In contrast, no significant perturbation in the insulin response to perfused glucagon was detected under conditions of low (4.4 mmol/l) or high (16.6 mmol/l) glucose in GLP-1R -/- mice. Total pancreatic insulin but not glucagon content was significantly reduced in GLP-1R -/- compared with in +/+ mice (77 +/- 9 vs. 121 +/- 10 pmol/mg protein; P < or = 0.005). These observations suggest that upregulation of the GIP component of the enteroinsular axis, at the levels of GIP secretion and action, modifies the phenotype resulting from interruption of the insulinotropic activity of GLP-1 in vivo.     

Dissociation between two forms of conceptual priming in Alzheimer's disease.

Patients with Alzheimer's disease (AD) and healthy control participants performed 2 conceptual repetition priming tasks, word-associate production and category -exemplar production. Both tasks had identical study-phases of reading target words aloud, had the most common responses as target items, and required production of a single response. Patients with AD showed normal priming on word-associate production but impaired priming on category-exemplar production. This dissociation in AD suggests that conceptual priming is not a unitary form of memory but rather is mediated by separable memory systems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Resistance of the insulinotropic action of alpha-D-glucose and beta-L-glucose pentaacetates to cholera and pertussis toxins

The pentaacetate esters of alpha-D-glucose and beta-L-glucose were recently reported to stimulate insulin release. The possible participation of G-protein-coupled receptors to the insulinotropic action of these esters was investigated in rat pancreatic islets either preincubated with cholera toxin or obtained from animals injected with pertussis toxin. Neither procedure affected adversely the secretory response to the esters in islets incubated in the presence of L-leucine. Thus, in both situations, alpha-D-glucose pentaacetate and, to a lesser extent, beta-L-glucose pentaacetate augmented insulin release evoked by the branched-chain amino acid, whilst beta-L-galactose pentaacetate failed to do so. These findings suggest that G-proteins sensitive to either cholera or pertussis toxins are not involved in one of the two modalities by which these esters are thought to stimulate insulin secretion, namely that independent of the catabolic fate of their hexose moieties.     

The insulinotropic action of gastric inhibitory polypeptide in the perfused isolated rat pancreas

Gastric inhibitory polypeptide (GIP) produced a dose-related increase in immunoreactive insulin (IRI) from the perfused isolated rat pancreas. The doses employed were within physiological limits. This effect was glucose-concentration-dependent in that there existed a threshold concentration of glucose above which GIP exerted the insulinotropic action, and that, at a fixed concentration of GIP, increased glucose concentrations stimulated IRI release in more than an additive manner. A biologically active fragment of the GIP molecule was isolated and purified. All criteria have been satisfied that GIP is an insulinotropic hormone.     

On the external validity of two psychotherapy analogues.

Investigated the similarity between 2 live psychotherapy analogs and real psychotherapeutic interviews. 23 therapists participated in 2 different types of analog situations and in initial intake sessions with real clients. In both of the analogs, a recruited S presented a real personal problem to the therapists in helping interactions. Audiotapes of the real and analog interviews were rated on 10 dependent variables, which were different dimensions of therapist and client behaviors. Different results were obtained for each analog. The major findings concern mean differences between the analog and real interviews and the linear relationships between the real and analog interviews. Additional findings, including significant interactions between the type of interview and the experience level of the therapist, are also discussed. Results indicate that the generalizability of the analogs is contingent on the dependent variables in question, the type of relationship to be predicted, and the experience level of the therapists. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evidence for contribution by increased cytoplasmic Na+ to the insulinotropic action of PACAP38 in HIT-T15 cells

Pituitary adenylate cyclase-activating polypeptide (PACAP) is localized to pancreatic nerve terminals and stimulates insulin secretion. The insulinotropic effect of PACAP38 in insulin-producing HIT-T15 cells is accompanied by increases in cellular cAMP and cytoplasmic Ca2+ ([Ca2+]cyt). As also intracellular Na+ is important for insulin secretion after glucose and other cAMP forming peptides, we examined the Na+ dependence of the insulinotropic effect of PACAP38 in HIT-T15 cells. We found that PACAP38 (100 nM)-induced insulin secretion was diminished by approximately 50% by removal of extracellular Na+ (replaced by equimolar N-methyl-D-glucamine). In contrast, removal of Na+ did not diminish the formation of cellular cAMP (measured by radioimmunoassay) or the increase in [Ca2+]cyt (measured in FURA-2AM-loaded cell suspensions) induced by PACAP38. Furthermore, PACAP-38 increased the cytoplasmic Na+ ([Na+]cyt) in single HIT-T15 cells as measured by the fluorophore sodium-binding benzofran isophthalate. This increase was reduced by removal of extracellular Na+ and by inhibition of protein kinase A by H-89. We conclude that the insulinotropic action of PACAP38 is Na+-dependent. We propose that PACAP38 opens plasma membrane Na+ channels by an action partially mediated by cAMP and protein kinase A, and the subsequent raise in [Na+]cyt elicits insulin secretion by an as yet unsolved mechanism.     

Dissociation between location and shape in visual space.

There are often large perceptual distortions of shapes lying on the ground plane, even in well-lit environments. These distortions occur under conditions for which the perception of location is accurate. Four hypotheses are considered for reconciling these seemingly paradoxical results, after which 2 experiments are reported that lend further support to 1 of them-that perception of shape and perception of location are sometimes dissociable. The 2 experiments show that whereas perception of location does not depend on whether viewing is monocular or binocular (when other distance cues are abundant), perception of shape becomes more veridical when viewing is binocular. This means that perception of shape is not fully constrained by the perceived locations of the vertices that define the shape. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A comparison of two types of counseling analogues.

Compared Ss' attraction to the counselor, self-reported and physiological anxiety, and susceptibility to persuasion, using 2 types of counseling analogs, quasi-counseling, and vicarious participation. Ss were 85 undergraduates. Participants in the quasi-counseling analog were significantly more attracted to the counselor than were vicarious-participation Ss. An attempt to indirectly structure perception of counselor empathy was unsuccessful in both analogs. The need for greater delineation of counselor and counseling process variables appropriate for different types of analogs is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prediction of carcinogenicity from two versus four sex-species groups in the carcinogenic potency database

Prediction of a positive result in rodent carcinogenesis bioassays using two instead of four sex-species groups is examined for the subset of chemicals in the Carcinogenic Potency Database that have been tested in four sex-species groups and are positive in at least one (n = 212). Under the conditions of these bioassays, a very high proportion of rodent carcinogens that are identified as positive by tests in four groups is also identified by results from one sex of each species (86-92%). Additionally, chemicals that are classified as "two-species carcinogens" or "multiple-site carcinogens" on the basis of results from four sex-species groups are also identified as two-species or multiple-site carcinogens on the basis of two sex-species groups. Carcinogenic potency (TD50) values for the most potent target site are similar when based on results from two compared to four sex-species groups. Eighty-five percent of the potency values are within a factor of 2 of those obtained from tests in 4 sex-species groups, 94% are within a factor of 4, and 98% are within a factor of 10. This result is expected because carcinogenic potency values are constrained to a narrow range about the maximum dose tested in a bioassay, and the maximum doses administered to rats and mice are highly correlated and similar in dose level. Information that can be known in advance of a 2-yr bioassay (mutagenicity, class, route, and maximum dose to test) does not identify groups of rodent carcinogens for which four sex-species groups are required to identify carcinogenicity. The range of accurate prediction of carcinogenicity using only male rats and female mice is 93% among mutagens and 88% among nonmutagens; for various routes of administration, 88-100%; for various chemical classes, 75-100%; and for various levels of the maximum dose tested, 81-100%. Results are similar for the pair male rats and male mice. Using a strength of evidence approach, weaker carcinogens are somewhat less likely than stronger carcinogens to be identified by two sex-species groups. Strength of evidence is measured using the proportion of experiments on a chemical that are positive, the extent to which tumors occur in animals that die before terminal sacrifice, and whether the chemical induces tumors at more than one site and in more than one species.     

Dissociation between syntactic and semantic processing during idiom comprehension.

Syntactic and semantic processing of literal and idiomatic phrases were investigated with a priming procedure. In 3 experiments, participants named targets that were syntactically appropriate or inappropriate completions for semantically unrelated sentence contexts. Sentences ended with incomplete idioms (kick the…) and were biased for either a literal (ball) or an idiomatic (bucket) completion. Syntactically appropriate targets were named more quickly than inappropriate ones for both contextual biases, suggesting that syntactic analysis occurs for idioms. In a final experiment, targets were either concrete (expected) or abstract (unexpected) nouns. For literal sentences, the abstract targets were named more slowly than the concrete targets. In contrast, there was no concreteness effect for idiomatic sentences, suggesting that the literal meaning of the idiom is not processed. Overall, the results provide evidence for dissociation between syntactic and semantic processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociation between recency and span: Neuropsychological and experimental evidence.

This article reports dissociations between verbal span and the recency portion of the serial position curve in immediate free recall, in 2 neuropsychological case studies and in 3 experiments with normal participants. Patient A. N. presented with an impaired serial verbal span while showing an intact recency effect. The opposite pattern was observed in patient G. C., who despite a poor recency showed normal span in verbal serial recall tasks. Experiments 1 and 2 showed a recency effect with visually and auditory presented lists and written recall was resistant to the effects of articulatory suppression and of irrelevant speech, but was disrupted by the suffix effect. Experiment 3 showed that in contrast with recency, memory span was affected by articulatory suppression and irrelevant speech during presentation but not by a suffix. These findings are not consistent with the idea that span and recency measure aspects of the same memory system. Moreover, in clinical practice, they should not be used as equivalent alternatives. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fractality and reversibility of ferrous martensite

Martensite formation is characterized by a diffusionless structural phase transformation from austenite to martensite, associated with a considerable amount of lattice variant shear γ_γα ? 0.2. Ferrous martensite shows all possible features connected with the transformation. Different modes of initiation of the martensite formation are possible. The reasons for the burst phenomenon can be considered as an analogy to discontinuous yielding. The transformation only procedes if further thermodynamical driving force is provided by cooling or shear stress. In some cases fractal microstructures are formed in which several fragmentations can be recognized. In contrast to shape memory alloys, steels usually do not show reversibility of the reverse α → γ transformation. The factors which favour reversibility have been defined. Knowledge of these is necessary for the development of iron-base shape-memory alloys.     

Stimulation of insulin release and potentiation of the insulinotropic action of antidiabetic agents by 1,2,3-tri(methylsuccinyl)glycerol ester in anaesthetized rats

The study was designed to investigate the effect of creatine monohydrate ingestion (20 g daily for 5 days) on performance in 45 s maximal continuous jumping and in all-out treadmill running at 20 km x h(-1), (inclination 5 degrees, duration approximately 60s). The participants were qualified sprinters and jumpers. The effect of creatine was compared with placebo in a double-blind design. Creatine (Cr) supplementation led to a significant enhancement of performance capacity in the jumping test by 7% during the first 15 s and by 12% during the second 15 s of the exercise. The positive effect of Cr supplementation was not observed in the last third of the continuous jumping exercise, when the contribution of anaerobic metabolism was decreasing. The time of intensive running up to exhaustion improved by 13%. The results show that Cr supplementation helps to prolong the time during which the maximal rate of power output could be maintained.     

5'-Hydrogenphosphonates of anti-HIV nucleoside analogues revisited: controversial mode of action

The monomeric and symmetrical dimeric 5'-hydrogenphosphonate derivatives of AZT were prepared and evaluated for their inhibitory properties against HIV-1 in several cell lines. The synthesis of the compounds was achieved by reaction of AZT with in situ prepared phosphorus tris(imidazolide) or with phosphonic acid in the presence of pivaloyl chloride. The two title compounds showed in vitro anti-HIV activity similar to (but not better than) that of AZT in three cell lines which were not deficient in thymidine kinase. On the other hand they were inactive in CEM-TK- cells. Pharmacokinetic studies in several media corroborate the assumption that these compounds must not be considered as 'true antiviral agents', but that they act by releasing their nucleoside entity.     

The insulinotropic region of gastric inhibitory polypeptide; fragment analysis suggests the bioactive site lies between residues 19 and 30

9-(4-Hydroxybutyl)-N2-phenylguanine (HBPG) is a new viral thymidine kinase inhibitor that we tested for the ability to prevent recurrences of herpetic keratitis. Eighteen squirrel monkeys (Saimiri scuireus) were infected in both corneas with the Rodanus strain of herpes simplex virus type 1 (HSV-1). All corneas showed typical dendritic keratitis 3 days after infection, followed by spontaneous healing. On day 21, the monkeys were randomized into two coded groups and ocular examinations were begun. One group received intraperitoneal (i.p.) injections of HBPG, 150 mg/kg, in a corn oil suspension every 8 h, and the other group received i.p. injections of the corn oil vehicle only. On day 22, recurrences were induced by reducing the temperature of the room in the late afternoon so that a low of 18 degrees C was achieved during the night. After the morning treatment, room temperature was raised to the normal ambient temperature (24-27 degrees C), and treatment was discontinued. Treatment was reinstituted on day 27, the room temperature was lowered again on day 28, and treatment was again discontinued as before. Third and fourth cycles of treatment and cold stress were begun on days 34 and 69. Ocular examinations were continued until day 73, at which point the code was broken. We found that the HBPG treatment significantly reduced the number of corneas with recurrences during the treatment periods, compared with recurrences in untreated, cold-stressed animals (P = 0.01).     

Dissociation between bone resorption and bone formation in osteopenic transgenic mice

Bone mass is maintained constant in vertebrates through bone remodeling (BR). BR is characterized by osteoclastic resorption of preexisting bone followed by de novo bone formation by osteoblasts. This sequence of events and the fact that bone mass remains constant in physiological situation lead to the assumption that resorption and formation are regulated by each other during BR. Recent evidence shows that cells of the osteoblastic lineage are involved in osteoclast differentiation. However, the existence of a functional link between the two activities, formation and resorption, has never been shown in vivo. To define the role of bone formation in the control of bone resorption, we generated an inducible osteoblast ablation mouse model. These mice developed a reversible osteopenia. Functional analyses showed that in the absence of bone formation, bone resorption continued to occur normally, leading to an osteoporosis of controllable severity, whose appearance could be prevented by an antiresorptive agent. This study establishes that bone formation and/or bone mass do not control the extent of bone resorption in vivo.     

Dissociation between the development of myocardial contracture and heart damage in the "calcium paradox"

The interrelationship between contracture development and heart damage during the calcium paradox under different sodium concentration in Ca-free media was studied on isolated rat hearts. It had been shown that calcium paradox development accompanied contracture development, intensive membrane disruption and alteration of tissue energy state. We had not found relation between contracture magnitude and degree of myocardial alterations in calcium paradox. Our dates confirm so-called intracellular hypothesis of calcium paradox. The experiments had shown close correlation between transmembrane sodium gradient in Ca-free media and degree of cellular damage and energy state alterations during calcium readmission in solution.     

Inhaled dry-powder formoterol and salmeterol in asthmatic patients: onset of action, duration of effect and potency

Salmeterol and formoterol are two long-acting beta2-agonists for inhalation, currently being used in clinical practice. The aim of the present study was to investigate the onset of action, duration of effect and potency of these two beta2-agonists in asthmatic patients. Patients (n=28) were included on the basis of salbutamol stepwise reversibility (100, 100 and 200 microg, given cumulatively; total reversibility > or =15%). In a double-blind placebo-controlled crossover study, the bronchodilating properties of formoterol 6, 12 and 24 microg were compared with the effects of salmeterol 50 microg. Formoterol was given via Turbuhaler and salmeterol via Diskhaler, and forced expiratory volume in one second (FEV1) was monitored during 12 h. Formoterol at all doses had a more rapid onset than salmeterol as judged from bronchodilation at 3 min after the dose. Formoterol at all doses had a similar duration of effect to salmeterol 50 microg, as judged from bronchodilation at 12 h after dose administration. When the relative potency of the two drugs was compared, salmeterol 50 microg was estimated to correspond to formoterol 9 microg (95% confidence interval: 3-19 microg). We confirm that formoterol and salmeterol are both long-acting beta2-agonists, but with some differences in effect profile. We confirm the more rapid onset of action of formoterol compared with salmeterol, and furthermore, no difference in duration of effect is evident.