Transient increase of blood histamine level induced by pentagastrin. Continuous monitoring by in vivo microdialysis

BACKGROUND: Since few studies of (penta)gastrin-induced histamine release from the gastric mucosa into blood has been performed, an effect of pentagastrin on histamine level of rat blood was examined by using the in vivo microdialysis method. METHODS: Pentagastrin was perfused through the microdialysis probe implanted into the jugular vein of urethane-anesthetized rats or in urethane-anesthetized, totally gastrectomized rats, and dialysis samples of blood were concurrently collected. Histidine decarboxylase (HDC) activities and histamine contents in the glandular stomach and gastric acid output after pentagastrin stimulation were also investigated. RESULTS: Pentagastrin induced a transient increase of blood histamine in a dose-dependent manner but failed to cause any increase of blood histamine in the totally gastrectomized rat. Pentagastrin also induced increases of the HDC activity in the glandular stomach and of the gastric acid output. The peak histamine level in blood occurred 40 min after pentagastrin perfusion, whereas the peak acid secretion occurred after 80-120 min and then leveled off. CONCLUSIONS: The transient increase of blood histamine induced by pentagastrin is attributable to the histamine released from enterochromaffin-like cells and could be monitored by using the in vivo microdialysis method.     

Changes in radiation sensitivity and steroid receptor content induced by hormonal agents and ionizing radiation in breast cancer cells in vitro

Possible influences of tamoxifen and estradiol on in vitro radiation sensitivity and cellular receptor content after irradiation and/or tamoxifen treatment were studied in breast cancer cell lines; estrogen receptor (ER) and progesterone receptor (PgR) positive cell lines MCF-7 and MCF-7/TAM(R)-1 and the ER and PgR negative cell line MDA-MB-231. The tamoxifen resistant MCF-7/TAM(R)-1 cells were more resistant to ionizing radiation than the MCF-7 and MDA-MB-231 cells. Exposure to tamoxifen made the MCF-7 cells more radiation resistant, while estradiol made the MDA-MB-231 cells more radiation sensitive. A radiation dose of 6 Gy reduced the ER content in cytosol in both MCF-7 and MCF-7/TAM(R)-1 cells, but brought no alterations to the PgR content. In MCF-7/TAM(R)-1 cells tamoxifen exposure significantly increased the ER and reduced the PgR content, an effect not observed in the MCF-7 cells. To conclude, the present study indicates that irradiation and tamoxifen may modify the ER and PgR content in cytosol in breast cancer cells. Hormonal treatment may alter the radiation sensitivity, even in ER negative cells, suggesting that hormonal agents may act both via receptor and non-receptor binding mechanisms.     

The role of ceramide in the cellular response to cytotoxic agents

STUDY AIM: The aim of this study was to report the results of pharyngoesophageal reconstruction in extensive corrosive strictures and to describe an original conception concerning extensive chemical burns of the pharynx with involvement of the epiglottis, oro-hypopharyngeal junction and cricopharyngeal pinchcock. PATIENTS AND METHODS: A personal series of 253 esophageal reconstructions using the colon and ileum is reported. In 124 patients, the cervical anastomosis of the graft was performed at the level of the pharynx, and these cases with extensive pharyngeal lesions were the basis of this study. The anastomosis was performed with the hypopharynx in 27 patients, with the oropharynx in nine and a total reconstruction of the pharynx or "pharyngoplasty" was carried out in 69 patients. The pharyngoplasty was classified according to the approach, in anterior, posterior, lateral, superior (transmandibular) and inferior. In high strictures with epiglottic injury, epiglottectomy was necessary in order to prevent recurrence. A visceral pharyngoplasty was performed in 61 patients, using the colon in 42 and the ileum in 19, a skin reconstruction in six patients and a myocutaneous flap in two. RESULTS: The global postoperative mortality rate was 4.7%. Stenosis of the cervical anastomosis occurred in 4.9% of the whole series. With a follow-up from 6 months to 10 years, 70% of the patients resumed a normal oral diet, 21% had mild symptoms and 7% had poor results (patients with tracheostomy and gastrostomy). CONCLUSION: Extensive chemical burns of the pharynx are very severe and their treatment very difficult. For the author, total visceral pharyngeal reconstruction is considered to be the procedure of choice, using ileopharyngoplasty with realization of an ileal pouch. Good results were obtained in 70% of the patients with extensive corrosive strictures.     

Pharmacokinetic parameters of genotoxic activity inferred from the comparison of the kinetics of MN-PCE induced by chemical agents and ionizing radiation

Some kinetic parameters of clastogenic activity of cyclophosphamide were inferred by means of the comparison of its kinetics of micronucleated polychromatic erythrocytes (MN-PCE) formation with the kinetics induced by radiation. The same reasoning was also applied to the kinetics obtained by treatment with mitomycin C (MMC), arabinocyl cytosine (Ara-C) and 6-mercaptopurine (6-MOP), based on previously reported data from the literature. The results indicate that the latency period (LP) and half-lives (HL) vary from one mutagen to another. For MMC, they are very similar to radiation indicating a rapid distribution and reaction. CP presents very long LP and HL which agree with the requirement of mutagen activation. Ara-C showed a very short LP which suggests a rapid activation and fast induction of damage in DNA. 6-MOP presented a very long LP which agreed with the requirement of its incorporation into DNA to cause micronucleus (MN). From the data obtained in the present work, it can be concluded that the comparison of the kinetics of MN-PCE formation induced by chemical agents with that obtained by the exposure to an acute dose of radiation permits one to estimate some parameters of the kinetics of clastogenic activity of chemical agents, like the LP and the HL. This seems to be valid for agents that act through the induction of DNA lesions; in the case of agents whose clastogenic activity is through other mechanisms, such as the inhibition or alteration of the process of duplication of the DNA, the kinetic parameters are not equivalent to the LP and HL; however, they could provide information on their possible mechanism of action.     

Peroxynitrite increases the degradation of aconitase and other cellular proteins by proteasome

We report that exposure of aconitase to moderate concentrations of peroxynitrite, 3-morpholinosydnonimine (SIN-1; a superoxide- and nitric oxide-liberating substance), or hydrogen peroxide, inhibits the enzyme and enhances susceptibility to proteolytic digestion by the isolated 20 S proteasome. Exposure to more severe levels of oxidative stress, from these same agents, causes further inhibition of the enzymatic activity of aconitase but actually decreases its proteolytic breakdown by proteasome. It should be noted that the superoxide and nitric oxide liberated by SIN-1 decomposition react to form a steady flux of peroxynitrite. S-Nitroso-N-acetylpenicillamine, a compound that liberates nitric oxide alone, causes only a small loss of aconitase activity (25% or less) and has no effect on the proteolytic susceptibility of the enzyme. Proteasome also seems to be the main protease in cell lysates that can degrade aconitase after it has been oxidatively modified by exposure to peroxynitrite, SIN-1, or hydrogen peroxide. Using cell lysates isolated from K562 cells treated for several days with an antisense oligodeoxynucleotide to the initiation codon region of the C2 subunit of proteasome (a treatment which diminishes proteasome activity by 50-60%), the enhanced degradation of moderately damaged aconitase was essentially abolished. Other model proteins as well as complex mixtures of proteins, such as cell lysates, also exhibit enhanced proteolytic susceptibility after moderate SIN-1 treatment. Therefore we conclude that peroxynitrite reacts readily with proteins and that mild modification by peroxynitrite results in selective recognition and degradation by proteasome.     

The epidemiology of the gastroduodenal damage induced by aspirin and other nonsteroidal anti-inflammatory drugs

A substantial body of studies (controlled, cohort and case-control studies) now confirm the long established impression that there is an increased prevalence of gastric and duodenal ulcer and of associated complications in subjects treated with aspirin (ASA) or with non-steroidal anti-inflammatory drugs (NSAIDs). The overall percentage of ulcers/erosions in patients treated with ASA ranges from 10 to 50% with a relative risk of bleeding ranging from 1.8 to 15%. The overall relative risk of ulcers/erosions in NSAIDs-treated subjects is around 3%, with complications detectable in 2.4% of cases. The risk of lesions and complications associated with ASA/NSAIDs is more marked in patients aged over 65, in those with a previous history of ulcer (both symptomatic and silent), in those treated with substantial doses or with combinations of NSAIDs and in those concomitantly using anticoagulants and/or steroids. The epidemiological data highlight the importance of implementing ASA/NSAIDs therapy only when strictly necessary as well as the advisability of adopting as broad a range of measures as possible to reduce the tissue-damaging effects of these pharmacological agents.     

Further investigation on the radiation induced inactivation of ribonuclease and the radioprotective effect of some selenium-containing compounds

Steady state inactivation data on dilute aqueous solutions of RNase show that all water radicals, e-aq, OH, and H are responsible for the inactivation, but the most efficient radical is H atom, only about 4 of them being required for one inactivating event. The data are, therefore, more in agreement with the conclusions of Mee et al. (1972). In the transient absorption spectra of pulse irradiated ribonuclease different components derived by the individual radicals are observed. Organic and inorganic selenium-containing compounds offer a great protection of the enzyme activity, in agreement with the data obtained in other chemical and biological systems. In particular the effects of two new secondary radicals (CNSe)-2 and SeO-3 are in good accord with the known structure of ribonuclease.     

Effect of some cyclooxygenase inhibitors on the increase in guanosine 3':5'-cyclic monophosphate induced by NO-donors in human whole platelets

1. The effect of the NSAIDs indomethacin, indoprofen, diclofenac and acetylsalicylic acid on the increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) induced by nitric oxide-donor agents was tested in human whole platelets and in platelet crude homogenate. 2. In whole platelets, indomethacin reduced the increase in cyclic GMP induced by the nitric oxide-donors (NO-donors) sodium nitroprusside (NaNP) and S-nitroso-N-acetylpenicillamine (SNAP) in a dose-dependent way, its IC50 being 13.7 microM and 15.8 microM, respectively. 3. Of the other cyclooxygenase inhibitors tested, only indoprofen reduced the increase in cyclic GMP induced by both NO-donors in a dose-dependent way (IC50=32.7 microM, NaNP and 25.0 microM, SNAP), while acetylsalicylic acid (up to 1000 microM) and diclofenac (up to 100 microM) were ineffective. 4. However, in platelet crude homogenate neither indomethacin nor indoprofen reduced the cyclic GMP production. 5. Indomethacin (10 microM), indoprofen (30 microM), diclofenac (100 microM) and acetylsalicylic acid (1000 microM) showed a comparable efficacy in inhibiting platelet thromboxane B2 (TXB2) production, suggesting that the inhibitory effect of indomethacin and indoprofen on the increase in cyclic GMP induced by both NO-donors was not mediated by inhibition of cyclooxygenase. 6. In vitro, the NSAIDs analysed did not interfere with nitrite production of SNAP. 7. The unhomogeneous behaviour of NSAIDs on the increase in cyclic GMP induced by NO-donors in whole platelets may contribute to the different pharmacological and toxicological characteristics of the drugs, providing new knowledge on the effect of indomethacin and indoprofen.     

Evaluation of the effect on heart rate variability of some agents acting at the beta-adrenoceptor using nonlinear scatterplot and sequence methods

There is evidence that the processes regulating heart rate variability (HRV) reflect nonlinear complexity and show "chaotic" determinism. Data analyses using nonlinear methods may therefore reveal patterns not apparent with the standard methods for HRV analysis. We have consequently used two nonlinear methods, the Poincaré plot (scatterplot) and cardiac sequence (quadrant) analysis, in addition to the standard time-domain summary statistics, during a normal volunteer investigation of the effects on HRV of some agents acting at the cardiac beta-adrenoceptor. Under double-blind and randomized conditions (Latin square design), 25 normal volunteers received placebo, salbutamol 8 mg (beta 2-adrenoceptor partial agonist), pindolol 10 mg (beta 2-adrenoceptor partial agonist), or atenolol 50 mg (beta 1-adrenoceptor antagonist). Single oral doses of medication (at weekly intervals) were administered at 22:30 hours, with sleeping heart rates recorded overnight. The long-term (SDNN, SDANN) and short-term (rMSSD) time-domain summary statistics were reduced by salbutamol 8 mg and increased by atenolol 50 mg compared with placebo. The reductions in both SDNN and SDANN were greater after salbutamol 8 mg compared with pindolol 10 mg. The reduced HRV after pindolol 10 mg differed from the increased HRV following atenolol 50 mg. The Poincaré plot, constructed by plotting each RR interval against the preceding RR interval, was measured using a reproducible computerized method. Scatterplot length and area were reduced by salbutamol 8 mg and increased by atenolol 50 mg compared with placebo; scatterplot length and area were lower after pindolol 10 mg compared with atenolol 50 mg. Geometric analysis of the scatterplots allowed width assessment (i.e., dispersion) at fixed RR intervals. At the higher percentiles (i.e., 90% of scatterplot length: low HR), salbutamol 8 mg reduced and atenolol 50 mg increased dispersion; at lower percentiles (i.e., 10%, 25%, and 50% length), atenolol 50 mg and pindolol 10 mg increased dispersion compared with placebo and salbutamol 8 mg. Cardiac sequence analysis (differences between three adjacent beats; delta RR vs. delta RRn + 1) was used to assess the short-term patterns of cardiac acceleration and deceleration. Four patterns were identified: +/+ (a lengthening sequencing), +/- or -/+ (balanced sequences), and finally -/- (a shortening sequence). Cardiac acceleration episodes (i.e., number of times delta RR and delta RRn + 1 were both changed) were increased in quadrants -/- and +/+ following pindolol 10 mg and salbutamol 8 mg; the beat-to-beat difference (delta RRn + 1) was reduced after salbutamol 8 mg compared with the three other groups. These results demonstrated a shift towards sympathetic dominance (beta-adrenoceptor partial agonist salbutamol 8 mg) or parasympathetic dominance (beta 1-adrenoceptor antagonist atenolol 50 mg); pindolol 10 mg exhibited HR-dependent effects, reducing HRV at low but increasing variability at high prevailing heart rates. These nonlinear methods appear to be valuable tools to investigate HRV in health and to study the implications of perturbation of HRV with drug therapy in disease states.     

Serum uric acid level of Thai individuals in comparison with the nutritional status and some other physical and biochemical parameters

Serum uric acid levels were measured in a total of 287 adults of Thai origin in Bangkok and the rural area. Mean values and range were found to exceed slightly serum uric acid concentration as reported from western countries. There was no significant difference between the Bangkok group and the group from the rural area but males and females differed significantly in their serum uric acid levels. A significant positive correlation to the ratio between weight to height as an index of the nutritional status was found.     

Does mentioning “some people” and “other people” in a survey question increase the accuracy of adolescents' self-reports?

A great deal of developmental research has relied on self-reports solicited using the “some/other” question format (“Some students think that… but other students think that…”). This article reports tests of the assumptions underlying its use: that it conveys to adolescents that socially undesirable attitudes, beliefs, or behaviors are not uncommon and legitimizes reporting them, yielding more valid self-reports than would be obtained by “direct” questions, which do not mention what other people think or do. A meta-analysis of 11 experiments embedded in four surveys of diverse samples of adolescents did not support the assumption that the some/other form increases validity. Although the some/other form led adolescents to think that undesirable attitudes, beliefs, or behaviors were more common and resulted in more reports of those attitudes and behaviors, answers to some/other questions were lower in criterion validity than were answers to direct questions. Because some/other questions take longer to ask and answer and require greater cognitive effort from participants (because they involve more words), and because they decrease measurement accuracy, the some/other question format seems best avoided. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Climbing the goal ladder: How upcoming actions increase level of aspiration.

Pursuing a series of progressive (e.g., professional) goals that form a goal ladder often leads to a trade-off between moving up to a more advanced level and repeating the same goal level. This article investigates how monitoring one's current goal in terms of remaining actions versus completed actions influences the desire to move up the goal ladder. The authors propose that a focus on remaining (vs. completed) actions increases the motivation to move up to a more advanced level, whereas the focus on completed (vs. remaining) actions increases the satisfaction derived from the present level. They find support for these predictions across several goal ladders, ranging from academic and professional ladders to simple, experimental tasks. They further find that individuals strategically attend to information about remaining (vs. completed) actions to prepare to move up the goal ladder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A comparison of taste aversions induced by radiation and lithium chloride in CS-US and US-CS paradigms.

Describes 3 experiments with a total of 454 albino male Charles-River rats. Conditioned taste aversions induced by ionizing radiation and lithium chloride (LiCl) were compared with both forward (CS-UCS, conditioned stimulus-unconditioned stimulus) and backward (UCS-CS) conditioning paradigms. Taste aversions were produced when a saccharin CS preceded or followed a 100-r radiation UCS by as much as 6 hrs, but a 2%-of-body-weight, .15-mol LiCl UCS was effective only in CS-UCS pairings. It is argued that the ineffectiveness of an LiCl stimulus in UCS-CS pairings was not attributable to differences in the "strength" of the respective LiCl and radiation doses in that these doses yielded comparable aversions in forward pairings. These results are related to inadequacies of a "sickness" model of taste aversion conditioning. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of some chelating agents on urinary copper excretion by the rat

In order to estimate the potential advantages of new chelating agents which can enhance copper excretion in the chronic copper intoxication arising in Wilson's disease, the relative ability of none chelating agents to induce the urinary excretion of copper was compared with that of D-penicillamine (DPA) and triethylenetetramine.2HCl (TRIEN), all given ip at 1 mmol/kg to male Sprague-Dawley rats. The compounds examined were as follows: tris(2-aminoethyl)-amine.3HCl (TREN), tetraethylenepentamine.5HCl (TETREN), pentaethylenehexamine.6HCl (PENTEN), 1,4,7,11-tetraazaundecane.4HCl (TAUD), 1,5,8,12-tetraazadodecane.4HCl (TADD), 1-N-benzyltriethylenetetramine.4HCl (BzTT), 4,7,10,13-tetraazatridecanoic acid.2H2SO4 (TTPA), 1,10-bis(2-pyridylmethyl)-1,4,7,10-tetraazadecane.4HCl (BPTETA), and N,N-bis(2-pyridylmethyl)-4-(aminomethyl)benzoic acid (4ABA). Of these, BzTT, TTPA, and 4ABA are new chelating agents not previously reported. The factors by which these chelating agents enhanced copper excretion over control (untreated) levels were as follows: DPA, 7.2; TREN, 1.6; TRIEN, 4.0; TETREN, 10.1; PENTEN, 7.8; TAUD, 7.8; TADD, 2.6; TTPA, 5.6; BzTT, 1.8; and 4ABA, 5.5. The results indicate that it may well be possible to develop additional chelating agents which are equal or superior to those now used in the treatment of Wilson's disease, as well as structural types whose immunological properties may be significantly different from DPA or TRIEN, the compounds currently used in the clinic for this disorder.     

Protection by acetylsalicylic acid and other agents in experimental acute interstitial pneumonia of calves

In experimental acute interstitial pneumonia caused by Ascaris suum, therapy with aspirin (acetylsalicylic acid) provided symptomatic control of the condition, reducing or abolishing the characteristic "setback". Treatment with antihistamines or antiserotonin agents caused no observable clinical improvements.     

Effects of level of cooperative choice by the other player on choices in a prisoner's dilemma game. Part II.

This study tests whether very high (or very low) cooperation by the other, sequential change in level of cooperation by the other, and degree of S's "flexible ethicality" will influence level of cooperative choice by 40 male and 40 female human Ss. The design is a mixed analysis of variance type with 3 independent and 2 nonindependent sources of variance. The main findings were that cooperative choice is influenced by a very high level of cooperation by the other, but even more by a sequence of low to high cooperation by the other. Flexible ethicality influences choice but in a complex association with sex and sequence. Essentially, then, communication is possible through reiteration of the Prisoner's Dilemma game. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The increase in angiotensin type-2 receptor mRNA level by glutamate stimulation in cultured rat cortical cells

Advanced practice nurses are challenged to assess comprehensively the value of their role and the impact of their practice. Value is defined as quality divided by cost. The correlations among the structure, strategies of care (process), and their objectives (outcome) are key to the assessment of the quality of care and the impact of the advanced practice nurse's role. Advanced practice nurses are challenged to provide high quality care for a competitive or decreased cost. For the profession of nursing, outcomes are the result of interventions based on the nurse's clinical judgment and theoretical, practical, or scientific knowledge. An evaluation model is presented that comprehensively measures the impact of advanced practice nurses on patients and families, and an example is presented. Using the model will give credibility and validity to the APNs' positive impact on the quality and financial outcomes of care for each patient and for entire patient populations.     

Calcium antagonists and prevention of ventricular fibrillation induced by transient or persistent ischemia

Experimental studies have shown the limitation by calcium antagonists of the propensity to fibrillation secondary to the occlusion of a large coronary artery. However, this capacity, studied in the acute phase of infarction, is less obvious and still under debate. Ischemia was therefore produced in anesthetized, open-chest pigs by complete occlusion of the left anterior descending coronary artery according to two modes, either near its origin during brief but increasing periods (30, 60, 120, 180 s, etc) or half-way from this origin for a much longer time (60 min). The time course of vulnerability to fibrillation was monitored by ventricular fibrillation threshold (VFT), measured by trains of diastolic stimuli of 100 ms. Verapamil was administered in a 50 micrograms/kg dose followed by 2 micrograms/kg/min infusion. 1) In the case of brief proximal occlusions under pacing at a constant high rate (180 beats/min), verapamil slowed the decline of VFT from 6-8 mA to nearly 0 mA. VFT was 4.4 +/- 0.4 mA after 60 s ischemia, whereas it had already fallen to 1.8 +/- 0.3 mA (p < 0.001) in the absence of the drug. Accordingly, the onset of spontaneous fibrillation which depends on the decrease in VFT to about 0 mA was prolonged from 2-3 to 6-9 min. Bradycardia, concurrently produced by verapamil, is a factor which enhances these alterations. 2) In the case of a persistent midportion occlusion of the artery under sinus rate, fibrillations were similarly delayed by verapamil from 14-25 to 23-49 min after occlusion, but they were more numerous. VFT was lowered to critical values later, but also for a longer time. The period propitious to fibrillation was prolonged because the return of VFT to higher values reflecting hypoexcitability subsequent to the first cell injury was substantially delayed. Consequently, calcium antagonists should often prevent ventricular fibrillation when transient ischemia disappears before VFT falls to the vicinity of 0 mA. In contrast, a real benefit could not be expected from these drugs when ischemia is persistent since they then only delay fibrillations, the number of which is increased.