bluuebunny/crossref_metadata_2025 huggingface dataset:
Protected‐Area Monitoring Dilemmas: a New Tool to Assess Success
Authors: WALKER KENDRA L.
Published: March 2009

Abstract:  Understanding factors that influence the success of protected areas in curbing unsustainable resource consumption is essential for determining best management strategies and allocating limited resources to those projects most likely to succeed. I used a law‐enforcement and monitoring game‐theory model from the political science literature to identify three key variables useful in predicting the success of a protected area: costs of monitoring for rule breakers, benefits of catching a rule breaker, and probability of catching a rule breaker if monitoring. Although assigning exact values for each of these variables was difficult, the variables had a strong predictive capacity even when coded as coarse ordinal values. A model in which such values were used correctly predicted the outcome of 88 of 116 protected areas sampled from the peer‐reviewed literature. The model identified a critical zone of common mismatch between protected‐area circumstances and management policies. In situations where the costs of monitoring were greater than the product of the probability of catching a rule breaker and the benefit of doing so, conservation was unlikely to succeed. Control of illegal use of protected resources was reported in only 8% of such cases, regardless of strategies to motivate potential users to cooperate with conservation. My model does not prescribe a best management policy for conserving natural resources; rather, it can be used as a tool to help predict whether a proposed management policy will likely succeed in a given situation.
An Author's Guide to Publication Ethics: A Review of Emerging Standards in Biomedical Journals
Authors: Roberts Jason
Published: March 2009

Universal definitions of ethical issues related to medical publishing have remained somewhat elusive. Training in the art of writing for medical journals is inconsistent and most commonly informal, involving collaborative efforts between mentors and students. This approach inadvertently may perpetuate erroneous assumptions as to what constitutes acceptable behavior. In contrast to instruction on composition, ethical considerations related to the publication of a paper are likely to receive little attention.

Even so, consequent to the ever‐increasing scrutiny from the media and government agencies, journals are recognizing the need for greater transparency in peer review and are thus more inclined to enforce ethical standards. Understanding that some apparent ethical contraventions are the result of confusion or a lack of knowledge, some journals are assuming the responsibility of educating their community about ethical issues in publishing. This paper reviews the key ethical issues (eg, authorship criteria, conflicts of interest, redundant publication, data access and biases in data reporting, image manipulation) that authors should consider before submitting a manuscript. It also surveys some of the policies of the most highly cited clinical medical journals. In the future, authors can anticipate that their submissions will be required to meet an expanding array of ethical standards.
Imaging of Language‐Related Brain Regions in Detoxified Alcoholics
Authors: Chanraud‐Guillermo Sandra , Andoh Jamila , Martelli Catherine , Artiges Eric , Pallier Christophe , Aubin Henri‐Jean , Martinot Jean‐Luc , Reynaud Michel
Published: March 2009

Background:  Neuroimaging studies showed clear evidence of alcoholism‐related damage to the frontal lobes and cerebellum. Although these regions have been involved in language processing, language skills are relatively spared in alcoholics. Here, we aimed at identifying neural substrates associated with the preserved mechanisms of language processing in alcoholics. We hypothesized that alcoholics would show a different pattern of neural activity compared with the controls.

Methods:  Alcoholic and nonalcoholic subjects performed an auditory language task while receiving a functional magnetic resonance imaging (fMRI) scan in a 1.5 T magnet. This task has been previously shown to solicit the comprehension processing in healthy controls, with reliable fMRI response in the left frontal and temporal/parietal lobes.

Results:  Behavioral results showed comparable performance (error rates, response time) between the alcoholics and the matched controls. However, analysis of the functional data revealed that the alcoholics exhibited greater fMRI response in the left middle frontal gyrus (pars triangularis), the right superior frontal gyrus, and the cerebellar vermis relative to the controls.

Conclusions:  These findings suggest that frontocerebellar neural activity, supporting the comprehension processing of the auditory language task, may require compensatory mechanisms in alcoholics in order to maintain the same level of performance as the controls.
Do Solicitations Matter in Bank Credit Ratings? Results from a Study of 72 Countries
Authors: POON WINNIE P. H. , LEE JUNSOO , GUP BENTON E.
Published: March 2009

Would the credit ratings of unsolicited banks be higher if they were solicited? Alternatively, would the credit ratings of solicited banks would be lower if they were unsolicited? To answer these questions, we use an endogenous regime‐switching model and data from 460 commercial banks in 72 countries, excluding the United States, for the period 1998–2003. The answer to both questions is yes. Our results show that the observed differences between solicited and unsolicited ratings can be explained by both the solicitation status and financial profile of the banks. This finding is a new contribution to the literature.
Real Wage Rigidities and the Cost of Disinflations
Authors: ASCARI GUIDO , MERKL CHRISTIAN
Published: March 2009

This paper analyzes the cost of disinflations under real wage rigidities in a micro‐founded New Keynesian model. The conventional view is that real wage rigidities can be a useful mechanism to generate a slump in output after a credible disinflationary policy because they prevent the immediate adjustment of inflation. This view is flawed, since it depends on analyzing the model in a linearized framework. Once nonlinearities are taken into account, the results change both qualitatively and quantitatively. Disinflations actually lead to a permanently higher level of output, and real wage rigidities increase the output during the adjustment to the new steady state.
A Short History of Price Level Convergence in Europe
Authors: FABER RIEMER P. , STOKMAN AD C. J.
Published: March 2009

We study the evolution of price level dispersion in Europe by combining time‐series information on harmonized indices of consumer prices (HICPs) with occasional observations of absolute price levels. We find that European price levels converged over much of the last 40 to 50 years. In the United States, our benchmark, price level dispersion is more or less stable. A back‐of‐the‐envelope calculation suggests that indirect tax rate harmonization, convergence of nontraded input costs, and convergence of traded input costs (in the form of exchange rate stability and increased openness) are all important in explaining European price level convergence.
Flexible Majority Rules for Central Banks
Authors: GERSBACH HANS , PACHL BERNHARD
Published: March 2009

We propose a flexible majority rule for central‐bank committees where the size of the majority depends monotonically on the change in interest rate within a particular time frame. Small changes in the interest rate require a small share, while larger changes require a larger share of supporting votes. We show that flexible majority rules are superior to simple majority rules.
Purdah—On the Rationale for Central Bank Silence around Policy Meetings
Authors: EHRMANN MICHAEL , FRATZSCHER MARCEL
Published: March 2009

Many central banks share the practice of purdah, a guideline of abstaining from communication around policy meetings. Although seemingly contradicting the virtue of transparency by withholding information precisely when it is sought after intensely, it has been justified on grounds that such communication may create excessive market volatility. This paper assesses the purdah for the Federal Reserve and confirms that financial markets are substantially more sensitive to central bank communication around policy meetings. Short‐term interest rates react three to four times more strongly in the purdah before Federal Open Market Committee meetings than otherwise, and volatility increases (compared to a reduction otherwise).
Comparison between Three‐Dimensional Angiographic Reconstruction and Intravascular Ultrasound Imaging for the Measurement of Cross‐Sectional Luminal Dimensions in Intermediate Coronary Lesions
Authors: COLLINGWOOD ROBIN , BERMUDEZ EDMUND , FISCHELL TIM A.
Published: March 2009

Background: Intravascular ultrasound (IVUS) has enabled the measurement of minimal luminal area of coronary stenoses. We evaluated the hypothesis that angiographic three‐dimensional reconstruction of luminal dimensions may be able to provide similar measurements to IVUS in intermediate coronary lesions.

Methods: We retrospectively enrolled patients undergoing invasive coronary angiography and IVUS for the assessment of angiographically intermediate coronary lesions (50–70%) at a high‐volume tertiary care hospital between July 1, 2006, and May 20, 2008. IVUS (
Boston Scientific, Natick Massachusetts, USA
) minimal cross‐sectional area (CSA) and minimal luminal diameters (MLD) were compared with the measurements obtained using a sophisticated three‐dimensional angiographic reconstruction software (CardiOP‐B, Paieon, Inc., Rosh Ha’ayin, Israel), with orthogonal angiographic views used to reconstruct and calculate lesion dimensions.

Results: Data were obtained from 34 patients with 35 lesions. The lesions were assessed in the left main (n = 2), left anterior descending artery (n = 15), left circumflex/marginal artery (n = 7), and right coronary artery (n = 11). Using IVUS, the mean minimal CSA was 3.78 ± 1.60 mm2, and MLD was 1.88 ± 0.43 mm. Three‐dimensional reconstruction measurements of minimal CSA (3.42 ± 1.66 mm2) highly correlated in a linear fashion with the measurements by IVUS (R = 0.88, P < 0.0001).

Conclusions: A three‐dimensional angiographic measurement of coronary minimal CSA is highly correlated with the measurements using IVUS. This new software technology may be a promising imaging modality to measure CSAs in coronary lesions.
Overexpression of malignancy‐associated laminins and laminin receptors by angiotropic human melanoma cells in a chick chorioallantoic membrane model
Authors: Lugassy Claire , Torres‐Muñoz Jorge E. , Kleinman Hynda K. , Ghanem Ghanem , Vernon Stephen , Barnhill Raymond L.
Published: March 2009

Background: As distinct from intravascular/lymphatic dissemination, extravascular migratory metastasis (EVMM) has been described as a potential additional mechanism of melanoma spread in which tumor cells migrate along the external surfaces of vessels. Angiotropic melanoma cells are linked to the endothelium by a matrix containing laminin. In addition, it has been shown that C16 laminin‐derived peptide increases extravascular migration of human green fluorescent protein (GFP) melanoma cells along vessels in a chicken chorioallantoic membrane model (CAM). In this study, we have tested the hypothesis that expression levels of some genes related to lamimin and metastasis are differentially expressed in vascularized angiotropic melanoma areas vs. avascular melanoma areas from the same tumor.

Design: C8161 human melanoma cells in a shell‐less chick CAM assay were used to study EVMM associated with the presence of vascularized angiotropic melanoma areas. For both high‐quality histomorphology and RNA preservation in paraffin‐embedded tissue, we used a methanol‐based fixative coupled with microwave‐assisted rapid tissue processing as previously described. Using laser capture microdissection, angiotropic melanoma areas as well as avascular areas were microdissected. Using quantitative real time polymerase chain reaction (QRT‐PCR), six genes have been studied: LAMC2 (laminin γ2 chain), LAMA4 (laminin α4 chain), ITGB1 (integrin β1), ITGB3 (integrin β3), RSPA (ribosomal protein), and MMP2 (matrix metallopeptidase 2). QRT‐PCR data were normalized to human GAPDH housekeeping gene and values were compared against Human Total RNA. Final results were expressed as percentage of expression.

Results: All tumors demonstrated a similar pattern, i.e. EVMM of angiotropic melanoma cells. The microdissected histopathological sections presented both angiotropic areas and avascular areas. All genes were overexpressed in angiotropic melanoma areas vs. avascular melanoma areas, especially LAMC2, LAMA4 and ITGB3 (respectively, 165.18, 208.86, and 483.69%).

Conclusion: This study shows that several genes related to laminin are overexpressed in angiotropic melanoma areas vs. avascular melanoma areas. Since extravascular migration of melanoma cells along vessels has been demonstrated in the CAM model, taken together these results suggests that some laminins and laminin receptors may play a role in extravascular migratory metastasis. This model may represent a promising strategy to analyze differential gene expression in EVMM.
Testicular choriocarcinoma metastatic to skin and multiple organs. Two case reports and review of literature
Authors: Chen Xinhua , Xu Linjie , Chen Xinmei , Teng Xiaodong , Zheng Shusen
Published: March 2009

Two cases of males with subcutaneous masses as the first clinical sign of testicular choriocarcinoma are reported. The urine and serum human chorionic gonadotropin (hCG) test confirmed high level hCG from male choriocarcinoma. These cases, although very rare, can be a great diagnostic and therapeutic challenge and should be considered in the differential diagnosis of subcutaneous masses occurring in young males.

Chen X, Xu L, Chen X, Teng X, Zheng S. Testicular choriocarcinoma metastatic to skin and multiple organs. Two case reports and review of literature.
Reduced numbers of circulating γδ T cells in patients with bullous pemphigoid
Authors: Oswald Eva , Fisch Paul , Jakob Thilo , Bruckner‐Tuderman Leena , Martin Stefan F. , Rensing‐Ehl Anne
Published: March 2009

Abstract:  Bullous pemphigoid (BP) is an autoimmune blistering skin disease characterized by autoantibodies to hemidesmosomal proteins. The initiation and regulation of the autoimmune response are poorly understood. We analysed cell subsets with immunoregulatory functions in untreated BP patients. While the numbers of circulating NKT and NK cells were normal, γδ T cells were reduced in BP patients. γδ T cells were rarely detected in lesional skin, arguing against their sequestration in the skin. In most patients, clinical remission and reduction of autoantibody titres after immunosuppressive therapy was not accompanied by an increase of circulating γδ T cells. Vγδ gene usage was not altered in BP patients and the γδ T cells of BP patients were functional as they proliferated in response to isopentenyl pyrophosphate. Our data provide a basis for further investigations on the role of γδ T cells in the immunopathogenesis of BP.
Sodium lauryl sulphate alters the mRNA expression of lipid‐metabolizing enzymes and PPAR signalling in normal human skin in vivo
Authors: Törmä Hans , Berne Berit
Published: March 2009

Abstract:  Detergents irritate skin and affect skin barrier homeostasis. In this study, healthy skin was exposed to 1% sodium lauryl sulphate (SLS) in water for 24 h. Biopsies were taken 6 h to 8 days post exposure. Lipid patterns were stained in situ and real‐time polymerase chain reaction (PCR) was used to examine mRNA expression of enzymes synthesizing barrier lipids, peroxisome proliferator‐activated receptors (PPAR) and lipoxygenases. The lipid pattern was disorganized from 6 h to 3 days after SLS exposure. Concomitant changes in mRNA expression included: (i) reduction, followed by induction, of ceramide‐generating β‐glucocerebrosidase, (ii) increase on day 1 of two other enzymes for ceramide biosynthesis and (iii) persistent reduction of acetyl‐CoA carboxylase‐B, a key enzyme in fatty acid synthesis. Surprisingly, the rate‐limiting enzyme in cholesterol synthesis, HMG‐CoA reductase, was unaltered. Among putative regulators of barrier lipids synthesis, PPARα and PPARγ exhibited reduced mRNA expression, while PPARβ/δ and LXRβ were unaltered. Epidermal lipoxygenase‐3, which may generate PPARα agonists, exhibited reduced expression. In conclusion, SLS induces reorganization of lipids in the stratum corneum, which play a role in detergents’ destruction of the barrier. The changes in mRNA expression of enzymes involved in synthesizing barrier lipids are probably important for the restoration of the barrier.
Tissue Electrolyte Changes Induced by High Doses of Diuretics in Rats
Authors: Borchgrevink P. C. , Holten T. , Jynge P.
Published: March 2009

Abstract:High doses of furosemide administered orally to growing rats for 4 weeks induced a pronounced fall in the concentration of magnesium and potassium in plasma, of magnesium in bone and potassium in skeletal muscle, but did not cause any reduction of these ions in the myocardium. The only electrolyte change in the heart of furosemide exposed rats was a higher calcium concentration than in rats of the control group. The addition of amiloride to furosemide in the ratio 1:16 mg corrected and partly overcorrected for the losses of magnesium and potassium in plasma and skeletal muscle. It is concluded that long term amiloride administration prevented magnesium and potassium losses induced by furosemide and that the myocardium was relatively resistant to furosemide induced magnesium and potassium loss.
Antibacterial Effect of Four Phenothiazines
Authors: Kristiansen Jette E. , Mortensen Ida
Published: March 2009

Abstract: Various types of phenothiazines were examined for antibacterial effect on 61 Gram‐positive and Gram‐negative bacterial strains in vitro. The investigated phenothiazines were two neuroleptic drugs, fluphenazine and chlorpromazine, and two antihistaminic drugs, alimemazine and promethazine. All four drugs have antibacterial effects in vitro, the phenothiazines being more potent against the Gram‐positive microorganisms. The antibacterial potency of the drugs was measured as IC50: Fluphenazine 29 μM (15 μg/ml), alimemzaine 49 μM (37 μg/ml), promethazine 88 μM (28 μg/ml) and chlorpromazine 92 μM (29 μg/ml). The antibacterial potency of the drugs was linked neither to the neuroleptic nor the antihistaminic potency of the drugs, which is in agreement with results of earlier stereoisomeric investigations. Thus, the known phenothiazines may represent a pool of potentially new antimicrobial drugs. A therapeutic application of these results, however, requires additional in vitro an in vivo testing in an animal model. The bacterial model might be of value as a model system in the study of the interaction of neuropharmacological agents and other membrane active compounds on biological membranes.
Substance K and Salivary Secretion in the Rat
Authors: Ekström J. , Månsson B. , Tobin G.
Published: March 2009

Abstract: Intravenous injections of substance K (SK), a novel member of the family of tachykinins, evoked secretion from the three major salivary glands of the rat in the presence of muscarinic, α‐adrenergic and β‐adrenergic receptor blockade; the submaxillary glands contributed most and the sublingual glands least to the total volume secreted. SK was less potent than substance P (SP) in evoking fluid and amylase secretion. However, the amylase concentration in parotid saliva evoked by SK was twice that evoked by SP, a finding which indicates that in the glands there are more than just one type of tachykinin receptors. Vasoactive intestinal peptide enhanced the SK evoked fluid response and increased the amylase concentration in parotid saliva. SK is a possible transmitter involved in the atropine‐resistant parasympathetic nerve evoked salivation in the rat.
Placental and Blood‐CSF Transfer of Intramuscularly Administered Atropine in the same Person
Authors: Kanto Jussi , Lindberg Raija , Pihlajamäki Kalevi , Scheinin Mika
Published: March 2009

Abstract: Both placental and blood‐CSF transfer of atropine (0.01 mg/kg intramuscularly) was measured (by RIA) in 11 parturients undergoing Caesarean section under spinal analgesia. In the foeto‐placental unit a significant penetration into amniotic fluid was found, whereas in CSF there was a measurable level of the drug (> 1.5 ng/ml) in only one mother. Our results show that there is a fundamental difference in the penetrability of tertiary ammonium alkaloids like atropine through these two biological membranes. However, our results concern penetration into human lumbar CSF and do not necessarily reflect potential penetration into the ventricular CSF, choroid plexus or brain ventricular ependyma.
Studies on the Effect of Different Inhibitors of Arachidonic Acid Metabolism on Glyceryltrinitrate‐induced Relaxation and cGMP Elevation in Bovine Vascular Tissue
Authors: Bornfeldt Karin E. , Axelsson Krister L.
Published: March 2009

Abstract:This study was performed in order to investigate the possible involvement of arachidonic acid metabolites in the mediation of glyceryltrinitrate (GTN)‐induced relaxation in isolated bovine mesenteric artery (BMA) and vein (BMV) and in bovine coronary artery (BCA). Concentration‐effect curves for GTN were established on the different types of vessels, precontracted with 2.5 μM phenylephrine (BMA) or K+‐depolarization (BMV and BCA), in the presence or absence of different inhibitors of the arachidonic acid metabolism. The used inhibitors of arachidonic acid metabolism were: 10 μM quinacrine (a phospholipase A2inhibitor), 100 μM acetylsalicylic acid, 20 μM indomethacin (cyclooxygenase inhibitors), 3 mM tranylcypromine (inhibitor of PGI2synthesis), 50 μM nordihydroguairetic acid and 40 μM BW 755C (lipoxygenase inhibitors). In addition, SKF 525A (10 μM) was tested on BMA; this agent is considered to block the cytochrome P450‐dependent monooxygenase pathway. The effect on the endogenous levels of cyclic nucleotides after treatment with some of the inhibitors were also measured. Quinacrine and acetylsalicylic acid had no statistical significant effect (P>0.05) on the pD2‐value for GTN‐induced relaxation in BMA, BMV and BCA. The results obtained with indomethacin were very variable. This drug was almost completely without effect on the GTN induced relaxation in BCA. In BMA a significantpotentiationof the relaxant response was obtained (P = 0.002), while in BMV a significant inhibition was seen (P = 0.049). Tranylcypromine and nordihydroguairetic acid were without statistical significant effect (P>0.1) on the GTN‐relaxation in BMA. Tranylcypromine caused a statistical significantpotentiationof the GTN‐response in both BCA and BMV (P = 0.003 and P = 0.00008, respectively). Nordihydroguairetic acidpotentiatedthe relaxant response in BMV (P = 0.01). Nordihydroguairetic acid also tended topotentiateGTN‐relaxations in BCA, although this effect did not reach the level of statistical significance (P = 0.074). A similar tendency towards apotentiatedrelaxant response was also seen for BW 755C in all of the vessel segments tested (0.1 <P<0.05). The basal levels of cyclic nucleotides were not significantly affected by any of the inhibitors tested, which included quinacrine, acetylsalicylic acid and nordihydroguairetic acid. Similarly, the GTN‐induced cGMP elevation was not significantly changed by these inhibitors. The present study implies that the arachidonic acid metabolites are without any major significance for the vasorelaxant effect of GTN in isolated peripheral arteries and veins and in coronary arteries. However, since several inhibitors potentiated the GTN‐induced relaxation a modulatory role of arachidonic acid metabolites in GTN‐induced vascular smooth muscle relaxation can not be excluded.
Metabolization of 14C‐N‐Acetylpenicillamine and 14C‐Cysteine in Relation to 1‐Chloro‐2,4‐dinitrobenzene and Sulphobromophtalein Conjugation and Biliary Excretion in the Rat
Authors: Refsvik Tor
Published: March 2009

Abstract: Upon intraperitoneal administrationof N‐(1‐14C)‐acetylpenicillamine (NAPA) to rats, at a dose of 1‐2 mmol/ kg body weight, a 14C‐labelled metabolite of NAPA together with unchanged NAPA were excreted in bile. The NAPA metabolite was characterized by acid hydrolysis and thin‐layer chromatography. Rats previously depleted of liver glutathione by intraperitoneal injection of cyclohexene oxide. 2.5 mmol/kg body weight, were given intraperitoneal injections of 14C‐cysteine, 0.5mmol/kg, or14C‐NAPA, 1‐2 mmol/kg, together with 1‐chloro‐2,4‐dinitrobenzene (DNB), 1 mmol/kg, or bromo‐sulphophtalein (BSP), 0.5 mmol/kg body weight. Simultaneous administration of 14C‐cysteine and DNB or BSP lead to rapid incorporation of 14C‐activity in glutathione and glutathione conjugates of DNB and BSP being excreted in bile. Upon simultaneous administration of 14C‐NAPA and DNB or BSP, 14C‐labelled metabolite of NAPA not conjugated to DNB or BSP, and unchanged NAPA, together with non‐labelled glutathione conjugates of DNB or BSP, were excreted in bile. This is interpreted as indicating that neither NAPA nor NAPA metabolite are capable of forming conjugates of DNB or BSP in rat liver.
Muscarinic Receptors Activate Calcium Channels and Calcium Dependent Potassium Channels in NIE‐115 Neuroblastoma Cells
Authors: Hedlund Britta , Lorentz Maud , Arhem Peter
Published: March 2009

Abstract: Responses of NIE‐115 neuroblastoma cells to application of carbachol were studied using intracellular recording techniques. Activation of muscarinic cholinergic receptors by carbachol resulted in a depolarization of the cells. The response was blocked by pirenzepine (1 μM) and by CoCl2 (5 mM), verapamil (10 μM) and gallopamil (10 μM), and prolonged by quinine (5 mM). It is suggested that muscarinic receptors increase the membrane calcium permeability, and that the influx of calcium activates calcium dependent potassium channels.
The Metabolite Ratio as a Function of Chloral Hydrate Dose and Intracellular Redox State in the Perfused Rat Liver
Authors: Kawamoto Toshihiro , Hobara Tatsuya , Kobayashi Haruo , Iwamoto Susumu , Sakai Tsunemi , Takano Takehito , Miyazaki Yoshifumi
Published: March 2009

Abstract:Chloral hydrate (CH), an intermediate metabolite of trichloroethylene, is reduced to trichloroethanol (TCE) by alcohol dehydrogenase and aldehyde reductase, and is also oxidized to trichloroacetic acid (TCA) by the nicotinamide adenine dinucleotide (NAD)‐dependent enzyme, CH dehydrogenase. Alcohol dehydrogenase requires reduced NAD (NADH), aldehyde reductase requires reduced nicotinamide adenine dinucleotide phosphate (NADPH) and CH dehydrogenase requires NAD to complete the reaction. It is unclear which reaction is predominant at the physiological redox level in intact liver cells. To study this question, we perfused the livers of well‐fed rats with Krebs‐Ringer buffer solution containing 0.1 mM pyruvate/1.0 mM lactate. The levels of TCE and TCA in the effluent were measured by gas chromatography, and the fluorescence of reduced pyridine nucleotides was measured with a surface fluorometer. When a low concentration (below 0.25 mM) of CH was administered, more TCA than TCE was produced. When a high concentration of CH was administered (over 0.5 mM), TCE production was greater. Reduced pyridine nucleotides decreased inversely with the CH concentration. Even at low CH concentrations, pyridine nucleotides were not reduced. When 10 mM lactate was added to the perfusate in order to reduce the pyridine nucleotides in the liver cells, the TCE/TCA ratio increased. On the other hand, the TCE/TCA ratio tended to fall following the addition of 5.0 mM pyruvate. In conclusion, the TCE/TCA ratio was altered according to the concentration of CH, and to the redox level of pyridine nucleotides in the liver.
High‐Dose Metoclopramide and Chlorpromazine in the Treatment of Cisplatin‐induced Emesis
Authors: Aasebø U. , Slørdal L. , Prytz P. S. , Aarbakke J. , Norway Tromse
Published: March 2009

Abstract: Twenty patients with lung cancer, treated with cisplatin and etoposide, were divided into two groups at random and given antiemetic therapy consisting of either high‐dose metoclopramide (MCL) intravenously (8 mg/kg over 7 hours) and chlorpromazine (CPZ) (50 mg orally), or a reduced dose of MCL (6 mg/kg over 7 hours) and CPZ (50 mg orally). Serum MCL concentrations were monitored during the infusions. In the two groups, 33% and 38% vomited during and after the courses, and antiemetic control was achieved in 83% and 75% of the patients. There was no significant difference between the groups, and side effects were negligible. MCL concentrations exceeded 0.7 μg/ml in all patients, with great inter‐individual variation.
Influence of Cadmium‐metallothionein Pretreatment on Tolerance of Rat Kidney Cortical Cells to Cadmium Toxicity in Vitro and in Vivo
Authors: Jin Taiyi , Nordberg Gunnar F. , Nordberg Monica
Published: March 2009

Abstract: Kidney cells were isolated from rats pretreated by daily subcutaneous doses of cadmium metallothionein (CdMT; 0.05‐0.2 mg Cd/kg x 5) and from non‐pretreated rats. Upon exposure to CdCl2 in vitro (0‐200 μg Cd/ml), a concentration dependent decrease in viability was observed in the non‐pretreated cells, while no such decrease occurred in the pretreated cells indicating that these cells were more resistant to the toxic action of cadmium. There was a higher in vitro uptake of Cd+2 and an increased metallothionein (MT) concentration in the pretreated cells (compared to nonpretrated cells). Subcellular distribution studies revealed that Cd was mainly recovered in the “cytosol” fraction. The higher total cadmium uptake in pretreated cells corresponded to an increase of Cd in “cytosol” and “nuclear” fractions. This observation may be explained by MT‐binding of Cd in the cells and is in accordance with a possible protective effect of induced MT in the pretreated cells. In order to assess whether pretreatment‐induced tolerance to cadmium toxicity – indicated by the cellular studies – could also be observed in vivo, some whole animal experiments were also performed. A dose‐related proteinuria was observed in non‐pretreated rats after a single subcutaneous administration of 109Cd‐MT at doses of 0.05 and 0.4 mg Cd/kg. Urinary total Cd, 109Cd and MT was also increased in a dose‐related fashion. Cadmium concentrations in kidney were dose related and reached 19 μg/g wet weight. In contrast, in animals repeatedly pretreated with CdMT according to 1), no proteinuria was observed after administration of the same single doses of 109CdMT Total Cd, 109Cd and particularly MT‐concentrations in urine were lower in such pretreated animals than in non‐pretreated ones in spite of the accumulation of higher tissue concentrations of total Cd (up to 80 μg/g). The pretreatment was thus shown to prevent some of the acute nephrotoxicity of CdMT, possibly by means of induction of MT synthesis.
Effects of Raclopride on Exploratory Locomotor Activity, Treadmill Locomotion, Conditioned Avoidance Behaviour and Catalepsy in Rats: Behavioural Profile Comparisons between Raclopride, Haloperidol and Preclamol
Authors: Hillegaart Viveka , Ahlenius Sven
Published: March 2009

Abstract: Raclopride, a new potential antipsychotic agent blocking central dopamine (D2) receptors, was found to suppress exploratory locomotor activity, treadmill locomotion and conditioned avoidance response in rats. The threshold dose for effects in these test situations was about 0.5 mg/kg intraperitoneally. A considerably higher dose, 16 mg/kg intraperitoneally, was needed to produce maximal catalepsy. Maximal effects were obtained within 1–2 hrs and the duration of the effect was 2–8 hrs, depending on the test situation. The behavioural profile of raclopride is different from the classic antipsychotic haloperidol, blocking central dopamine (DA) receptors, as well as from the partial DA agonist preclamol, which inhibits central DA neurotransmission by activating DA autoreceptors. Thus, although similar to haloperidol in other respects, comparatively high doses of raclopride are needed to produce catalepsy, indicating less propensity to produce severe extrapyramidal side effects. Raclopride and preclamol are about equipotent in suppressing exploratory locomotor activity. However, raclopride is more potent than preclamol in suppressing treadmill locomotion, conditioned avoidance behaviour and catalepsy.
Effects of Chronic Neuroleptic Treatment on Agonist Affinity States of the Dopamine‐D2receptor in the Rat Brain
Authors: Hall Håkan , Sällemark Maria
Published: March 2009

Abstract:The effects of repeated oral administration to rats of three antipsychotic compounds (haloperidol 1 μmol/kg, raclopride 5 μmol/kg and remoxipride 10 μmol/kg) on agonist affinity states of the dopamine‐D2receptor were studied using3H‐spiperone binding to rat striatal homogenatesin vitro.The competition between3H‐spiperone and dopamine was analyzed using the iterative nonlinear computer program LIGAND. The treatment of rats with haloperidol, raclopride and remoxipride caused an increased number of striatal dopamine‐D2receptors. In parallel to this increase in Bmax (approximately 50%) there was an increased fraction of the number of receptors being in the D2(high) affinity state. The affinity of dopamine for the D2(high) state was not affected while a significant decrease in affinity of dopamine for the D2(low) state was found. The results are discussed in view of the mechanism of action of the three compounds and of neuroleptics in general.
Effects of the Dopamine D2 Selective Receptor Antagonist Remoxipride on Dopamine Turnover in the Rat Brain after Acute and Repeated Administration
Authors: Magnusson Olle , Mohringe Bodil , Thorell Gun , Lake‐Bakaar Desmond M.
Published: March 2009

Abstract: The effects of the dopamine D2 selective receptor antagonist, remoxipride, on dopamine turnover in the rat brain were studied after acute and repeated administration and compared with the effects of haloperiodol. Acute administration of remoxipride produced a dose‐dependent increase of the concentrations of DOPAC and HVA in both striatum and olfactory tubercle+nucleus accumbens. The maximal effect of both acute remoxipride and haloperidol on dopamine turnover was attained approximately 2 hours after a single intraperitoneal administration, whereas a biphasic response was seen after oral remoxipride. Tolerance to the effects of repeated haloperidol (20 μmol/kg orally) treatment on dopamine turnover was observed as soon as after 3 days, whereas no such tolerance could be found during the first 15 days of repeated treatment with remoxipride (20 μmol/kg orally). A dose‐related tolerance to the effects of remoxipride was, however, seen at higher dosages (40, 150 and 600 μmol/kg orally) and after a longer period (6 months) of treatment.
Regional Differences in the Changes in Rat Brain GABA Concentrations Post Mortem and Following Inhibition of the Synthesis and Metabolism
Authors: Andén Nils‐Erik , Lindgren Silvana , Magnusson Åsa
Published: March 2009

Abstract: Experimentally induced changes in the concentration of GABA were studied in regions where GABA is present, predominantly in nerve terminals (substantia nigra, pituitary gland) or outside nerve terminals (corpus callosum). Some other regions (cerebellum, cuneate nucleus, corpus striatum, hippocampus) were included where the cellular localization of GABA is less certain. The post mortem increase in GABA was about equal percentagewise in all regions indicating that it occurs in all locations where GABA is present. The increase in GABA following the GABA α‐ketoglutaric acid aminotransferase inhibitor γ‐acetylenic GABA was much greater in the corpus callosum than in the other regions indicating that this enzyme is more important for the GABA present outside than inside the GABA nerve terminals. The glutamic acid decarboxylase inhibitor 4‐deoxypyridoxine decreased the endogenous concentration of GABA and it inhibited the increase in GABA induced by γ‐acetylenic GABA in the substantia nigra and in the pituitary gland, but not in the corpus callosum, indicating that this compound inhibits the decarboxylase mainly in the GABA nerve terminals.
Effect of Enzyme Induction and Inhibition on the Fate of Metronidazole and Tinidazole in the Rat
Authors: Männistö P. T. , Saijonmaa O. , Haataja H.
Published: March 2009

Abstract: The excretion routes of intact metronidazole and tinidazole were studied in rats kept in metabolism cages and cannulated for continuous bile collection. The nitroimidazoles were given intraarterially either alone or after a 5‐day pretreatment with phenobarbitone (70 mg/kg/day intravenously) or after a single dose of cimetidine (50 mg/kg intraarterially). After 30 mg/kg, 27.0% of the metronidazole dose was excreted intact in 24‐hr urine and 2.2% in bile. After tinidazole, the recoveries of the intact drug in urine and bile were 48.1% and 1.7%, respectively. After 90 mg/kg, the total recoveries of both drugs were 25‐28% smaller than after 30 mg/kg. Phenobarbitone pretreatment did not affect metronidazole levels in plasma but decreased tinidazole levels at 4 hrs. The 24‐hr recoveries of the intact nitroimidazoles in urine were significantly reduced by phenobarbitone while the 24‐hr bile recoveries were not. Cimetidine treatment enhanced both metronidazole (at 1, 2 and 3 hrs) and tinidazole (only at 1 hr) concentrations in plasma, but this shift was not reflected in the 24‐hr urine recoveries of the intact nitroimidazoles. Cimetidine doubled, however, the 24‐hr bile recovery of the intact tinidazole. The calculations of the apparent degree of metabolism, assuming no methodological losses, showed that phenobarbitone increased the metabolism of tinidazole by about 62% and that of metronidazole only by about 16%. The effect of a single dose of cimetidine was negligible.
Effects of Methyl Mercury on Testicular Functions in Macaca fascicularis Monkeys
Authors: Mohamed Mostafa K. , Burbacher Thomas M. , Mottet N. Karle
Published: March 2009

Abstract:These studies were performed to investigate the effects of MeHg on testicular function inMacaca fascicularismonkeys. In anin vivostudy involving oral treatment of adult malesMacaca fascicularismonkeys with MeHg for 20 weeks, changes in spermatozoal production, motility and morphology and in serum testosterone were followed before, during and after treatment. MeHg treatment significantly decreased% motile spermatozoa and scores for sperm speed and forward progression and increased % abnormal sperm tail forms, at sub‐neurotoxic levels. The MeHg‐induced increase in semen abnormalities was not accompanied by any significant changes in serum levels of testosterone. No consistent histological abnormalities were detected in testicular biopsies from the treated animals at the end of the treatment period. A good recovery pattern was observed for the MeHg effects on sperm motility while this was unclear for the effects on sperm morphology.
5‐Hydroxytryptamine Antagonists and the 5‐Methoxy‐N,N‐dimethyltryptamine‐induced Changes of Postdecapitation Convulsions
Authors: Archer Trevor
Published: March 2009

Abstract:The ability of various compounds to antagonise the 5‐MeODMT induced prolongations of latency and duration of postdecapitation convulsions (PDCs) were compared. The 5‐hydroxytryptamine (5‐HT) receptor antagonists, mianserin, methergoline, cinanserin and methysergide antagonised the 5‐MeODMT (0.5 to 4.0 mg/kg) induced prolongations of latency to onset of convulsions substantially and to a lesser extent the prolongation of duration. The efficacy of the 5‐HT antagonists for blocking 5‐MeODMT changes of PDCs was roughly of the order mianserin > cinanserin > methysergide > methergoline. Pirenperone, the 5‐HT2antagonist, and pimozide, the dopamine receptor antagonist did not antagonise the 5‐MeODMT induced changes. Mianserin, methergoline, cinanserin and methysergide, by themselves, prolonged the duration of PDCs but did not affect latency. Pirenperone (0.25 mg/kg) prolonged both the latency and duration of the PDCs while pimozide (0.5‐2.0 mg/kg) had no effect upon PDCs. This evidence suggests that 5‐MeODMT induced changes of PDCs are mediated via 5‐HT1receptors and thus a reliable model to combine with other measures of spinal function is suggested.
Carcinogen Metabolizing Enzymes in Nude Mice
Authors: Laaksonen A. Mariitta , Julkunen Antero
Published: March 2009

Abstract:Hepatic and cutaneous microsomal hydroxylating and conjugating enzymes from female and male NMRInu/numice were analyzed, and the response of these enzymes to repeated exposures with 3‐methylcholanthrene were studied. Sex differences were observed in basal activities of hydroxylating enzymes. These differences were not the same in the liver as in the skin and were reversed in female and male. Activity ratios of hepatic and cutaneous hydroxylating enzymes were between 40‐200. The ratios between hydroxylating and conjugating enzymes were much lower in the skin than in liver. Furthermore the ratios were depending on hydroxylating enzymes. 3‐Methylcholanthrene treatment increased both hydroxylating and conjugating enzymes in the liver and in the skin. Again, there were sex differences in the induction pattern, and also the induction in the liver was unrelated to that in the skin. There was no correlation in induction between hydroxylating and conjugating enzymes.
Interaction of Psychotropic Drugs with Brain Muscarinic Cholinoceptors: Similarities of Biperiden with Pirenzepine in Receptor Binding Properties
Authors: Syvälahti E. K. G. , Laurén L. , Markkanen J. , Kunelius R.
Published: March 2009

Abstract: It is generally accepted that there are at least three different subtypes of muscarinic cholinoceptors, pirenzepine being considered a selective M1 antagonist. In the present study, a number of different types of psychotropic drugs have been compared with pirenzepine and atropine as reference antimuscarinic drugs regarding their affinities for rat brain muscarinic cholinoceptors with the help of in vitro receptor binding studies. The most potent drugs, inhibiting 3H‐1‐quinuclidinyl benzilate (3H‐QNB) binding at subnanomolar concentrations, were the antimuscarinic drugs scopolamine and atropine. Biperiden, promethazine, pirenzepine and some tricyclic antidepressants (amitriptyline, doxepin) were the next potent drugs, with IC50‐values between 8.4 nM and 190 nM. The inhibition curves were steep and parallel giving Hill coefficients close to unity in all but two drugs studied. These exceptions were biperiden and pirenzepine both with Hill coefficients about 0.55. Thus, in addition to pirenzepine also biperiden seems to bind to the M1 receptor selectively. Additional receptor and functional studies are warranted to further elucidate the possible similarities of these two drugs.
Effects of Serotonin and Noradrenaline Uptake Blockers on Wakefulness and Sleep in Cats
Authors: Hilakivi I. , Kovala T. , Leppävuori A. , Shvaloff A.
Published: March 2009

Abstract: The aim of the study was to examine the role of serotonergic (5‐HT) and noradrenergic mechanisms in the regulation of wakefulness and sleep. For this purpose, adult cats with implanted electrodes for EEG, EOG and EMG were exposed to the 5‐HT uptake blocker citalopram (0.1, 0.5 and 5.0 mg/kg intraperitoneally) and the noradrenaline uptake blocker prindamine (5 mg/kg intraperitoneally) at the start of continuous 16‐hour sleep‐wake recordings. Citalopram increased deep slow wave sleep and decreased REMS. Also prindamine decreased REMS but initially increased the proportion of time spent in the state of active wakefulness. Furthermore, to examine the interactions between 5‐HT‐nergic and noradrenergic mechanisms in the regulation of sleep, the administration of citalopram was preceded by intraperitoneal injections of phentolamine (10 mg/kg), an α‐antagonist, and propranolol (5 mg/kg), a β‐antagonist. Phentolamine was totally ineffective against citalopram whereas propranolol partially counteracted the effects of citalopram on sleep. Prindamine was combined with the β‐antagonists yohimbine (1 mg/kg), phentolamine (10 mg/kg) and prazosin (1 mg/kg) or with the β‐antagonist propranolol (5 mg/kg). Yohimbine was without any effect on REMS, phentolamine partly antagonized prindamine‐induced decrease in the percentage of REMS, and prazosin only prolonged REMS latency and reduced deep SWS as well. Propranolol partially antagonized the prindamine‐induced initial increase in active wakefulness time. These results indicate that while both citalopram and prindamine suppress REMS, the concurrent increase in the amount of DSWS in the case of citalopram administration may be related to 5‐HT‐ergic mechanisms whereas the increase in active wakefulness occurring concurrently with inhibition of REMS in the case of prindamine administration may be related to noradrenergic mechanisms. The possible role of α‐ and β‐adrenoceptors in the mechanisms of the described drug interactions are discussed.
Early Biochemical and Histological Changes in Rats Exposed to a Single Injection of Thioacetamide
Authors: Dashti Hussein , Jeppsson Bengt , Hägerstrand Inga , Hultberg Björn , Srinivas Uppugunduri , Abdulla Mohammed , Joelsson Bo , Bengmark Stig
Published: March 2009

Abstract: Liver injury was induced by one subcutaneous administration of thioacetamide (200 mg/kg b.wt.) and studied 24 and 48 hrs later. Levels of aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) increased after 24 and 48 hrs. The lysosomal enzymes β‐hexosaminidase (β‐NAG) and β‐glucuronidase (β‐GLU) increased significantly after 24 hrs, while the level of β‐GLU returned to normal after 48 hrs, but the activity of β‐NAG remained significantly high even after 48 hrs. Histopathological examination showed necrotic hepatocytes around the central vein with infiltration of macrophages, neutrophils and eosinophils. The plasma zinc level decreased after 24 hrs and returned to normal after 48 hrs. Liver zinc content increased simultaneously at 24 hrs, returning to normal after 48 hrs. No alterations of plasma copper were observed after 24 and 48 hrs. Copper content of the liver increased significantly after 24 and 48 hrs. The present study thus shows that one dose of thioacetamide results in profound liver injury and supplementation of zinc prior to and simultaneously with thioacetamide normalized plasma zinc, increased liver zinc content and reduced the increase of β‐NAG, but did not influence the histological changes.
The Effect of Soman on Potassium Evoked 3H‐Acetylcholine Release in the Isolated Rat Bronchi
Authors: Aas Pål , Malmei Tore , Fonnum Frode
Published: March 2009

Abstract: The in vitro exposure of rat bronchial smooth muscle to the acetylcholinesterase inhibitor soman (0‐[1,1,2‐trimethylpropyl]‐methylphosphonofluoridate) reduced the potassium (51 mM) evoked release of 3H‐acetylcholine (3H‐ACh). Exposure to 1.0 and 100 μM soman for 15 min inhibited the acetylcholinesterase (AChE) activity completely and reduced the potassium evoked release by 23.1% and 34.4% respectively. In the presence of scopolamine (0.3 μM), however, there was a large enchement (87.0%) of potassium evoked release during soman inhibited (100%) AChE‐activity. Furthermore, soman (1.0 μM) did not reduce the spontaneous release of 3H‐ACh. The results indicate that the presynaptic effect of soman is due to the enhanced concentration of ACh following AChE‐activity inhibition in the synaptic region. This induces a stimulation of presynaptic muscarinic receptors and thereby modulation of the ACh release only during evoked release.