bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidative and Conjugative Metabolism of p–Nitroanisole and p–Nitrophenol in Isolated Rat Liver Cells
Authors: Moldéus Peter , Vadi Helena , Berggren Margareta 
Published: July 2010

Abstract Isolated rat liver cells were used in the study of p–nitroanisole and p–nitrophenol metabolism. p–Nitroanisole was o–dealkylated to form p–nitrophenol which was subsequently conjugated to form predominantly sulphate esters and β–glucuronides.1. At low concentrations of p–nitrophenol, sulphate conjugation was predominant but with increasing substrate concentration the glucuronidation activity was increased. At 250 μM p–nitrophenol the major conjugate formed was glucuronide while sulphate conjugation was inhibited.2. With p–nitroanisole in low concentration, resulting in low oxidation rate, all the p–nitrophenol formed was further conjugated to sulphate esters. With higher phenol production, glucuronide conjugates were also formed.3. Phenobarbital treatment of the rats increased the rate of p–nitroanisole oxidation by more than four times but had very little effect on the conjugation reactions. In these cells the major conjugate formed was glucuronide.4. The rate of glucuronidation in the isolated liver cells was higher than in microsomes and responded differently to various inhibitors. Alprenolol, a substrate of the hepatic mono–oxygenase system, had no inhibitory effect on glucuronidation in microsomes in the absence of NADPH. However, low concentrations of alprenolol showed similar inhibitory effects in microsomes in the presence of NADPH as in isolated liver cells.5. Nitrophenol glucuronide was strongly inhibitory to the glucuronidation in microsomes while almost no inhibition was observed in the isolated liver cells, probably due to poor penetration of the glucuronide through the cell membrane.6. Rotenone, menadione and ethanol had little effect in microsomes but were potent inhibitors of glucuronidation in the isolated liver cells, most probably by interfering with the synthesis of UDPGlcA.The effect of ethanol was maximal at as low a concentration as 10 mM and was shown to be due to alcohol dehydrogenase–dependent ethanol oxidation. The inhibition was presumably caused by the the increased cytoplasmic NADH/NAD4 ratio resulting from the metabolism of ethanol.
The Adrenergic Innervation of the Urinary Bladder in the Cat and Man in the Normal State and After Parasympathetic Denervation
Authors: Dahlström Annica 
Published: July 2010

Abstract The adrenergic innervation of the feline and human urinary bladder was studied with the histochemical fluorescence method of Hillarp and Falck. In the normal bladder of both species the trigone area was densely innervated by thick and strongly green‐fluorescent adrenergic terminals while the detrusor muscle contained a sparse innervation of very thin and weakly fluorescent nerve terminals.After parasympathetic denervation (lower motor neuron lesion in patients) the adrenergic innervation of the detrusor muscle was altered. In the cat, the first signs of altered adrenergic innervation were observed 6 weeks after parasympathetic denervation, when thick, strongly fluorescent adrenergic fibres appeared between and in the smooth muscle bundles. These fibres had the characteristics of growth cones and indicated an outgrowth of new adrenergic fibres into the detrusor muscle. Later on, the muscle bundles were densely innervated by thick and strongly fluorescent terminals, reminiscent of trigone terminals. In the patients with lower motor neuron lesions, thick, strongly fluorescent adrenergic terminals were seen in the detrusor. In both cat and man the appearance of this “new” type of adrenergic nerve terminal in the detrusor muscle coincided with the presence of α‐adrenoceptor function (rather than the normal β‐adrenoceptor activity of the feline and human detrusor).
Adrenergic Innervation and Adrenergic Mechanisms A study of the human urethra
Authors: Ek Anders 
Published: July 2010

Abstract Adrenergic nerves studied by a histochemical method were uniformly distributed along the whole extent of the male and female urethra. Corresponding to the adrenergic innervation a preponderance of contraction‐mediating alpha‐adrenoceptors was found in vitro studying urethral strips and in vivo recording the urethral closure pressure profile (UCPP).Norephedrine significantly reduced incontinence and increased UCPP in stress‐incontinent women.
Neurochemical and Behavioural Effects of Long‐term Intermittent Inhalation of Xylene Vapour and Simultaneous Ethanol Intake
Authors: Savolainen H. , Pfäffli P. , Helojoki M. , Tengén M. 
Published: July 2010

Abstract Two‐month‐old male Wistar rats were exposed to 300 p.p.m. of xylene vapour with simultaneous ethanol ingestion for 5 to 18 weeks. Neurochemical effects of mere vapour inhalation included an increase in microsomal superoxide dismutase activity in brain at the end of the experiment. Concomitant ethanol ingestion added significantly to the xylene‐induced effects by causing increased proteolysis at the 9th and 14th week of exposure whereas cerebral superoxide dismutase failed to increase in these animals.Preening frequency decreased transiently in ethanol and in xylene groups at 6 and 9 to 12 weeks, respectively, whereas increased ambulation occurred only in the xylene ‐ ethanol group after 12 and 14 weeks of exposure. The behavioural effects were therefore different in the combined exposure, and our biochemical and behavioural observations may point at significant interaction of both solvents although the biochemical mechanisms remain largely unexplained.
Methodological Aspects of Acute Toxicity Testing Particularly LD50 Determinations Present use in Development of New Drugs
Authors: Fowler J.S.L. , Rutty D.A. 
Published: July 2010

Abstract It is essential to have an adequate understanding of the acute toxic effects of a new drug. It may not be necessary however to blindly follow the full classical median lethal assay on every occasion.The LD50 was developed to obtain the maximum accuracy from a modest experimental size. The objective of the study and the limitations of the assay should not be overlooked however and undue precision should not be sought.Methodological aspects including species and maximum and minimum doses will be discussed.Other methods and approaches to acute toxicity will be recommended with a more broad approach to acute toxicity than lethality alone.
Predictive Acute Toxicity Tests With Pesticides.
Authors: Brown V. K. 
Published: July 2010

Abstract By definition pesticides are biocidal products and this implies a probability that pesticides may be acutely toxic to species other than the designated target species.The ways in which pesticides are manufactured, formulated, packaged, distributed and used necessitates a potential for the exposure of non‐target species although the technology exists to minimize adventitious exposure. The occurrence of deliberate exposure of non‐target species due to the misuse of pesticides is known to happen.The array of predictive acute toxicity tests carried out on pesticides and involving the use of laboratory animals can be justified as providing data on which hazard assessment can be based. This paper addresses the justification and rationale of this statement.
The use of acute toxicity data in poison information centres.
Authors: Werner B. 
Published: July 2010

Abstract Of the various animal test data the poison information centres consider the eye and skin irritation tests to be useful and the findings transferreble to man for evaluation of acute exposure risks.The LD50 and LC50 data are considered of doubtful value and even to involve some risks. Presented as uncommented figures, especially if placed alongside physical data on a chemical substance, they are given a nimbus of exactness that they are not entitled to because of the known reasons of species differences etc. LD50‐s are mortality data but what the poison information centres need are morbidity data. Doses lower than LD50 are as TD‐s therefore more of interest, provided they are given with a detailed description of the developing intoxication symptoms, preferrably also with information on the steepness of the dose‐symptoms curve. The facilities today to prevent death due to acute poisonings place the residual symptoms at survival more in the centre of interest and responsibility. Careful postmortems of the test animals are therefore also needed. Although examinations may have been performed on the animals killed by the LD50 dose they might have died too early for a late organ damage to appear (e.g. in paraquat poisoning the animal may die in kidney insufficiency which comes earlier than the obliteration of the bronchioli respiratorii) or the killing factor may be another than the one involved in the residual symptoms (e.g. CO‐poisoning, where COHb is the life‐limiting factor in gross exposure but does not seem to be related to the severe late CNS symptoms).When rating the toxicity of closely related but different compounds LD50 has some value.Suggestions: Symptoms developing at different TD‐s should be presented. Organs should be examined macro‐ and microscopically (had this been done the vacuoles in the CNS might have been seen early in the animal testing of hexachlorophene and human poisonings thereby prevented). The human poisoning cases — now not used to the extent they could be for drawing information regarding the poisoning — should be studied much more in detail and the information from different countries pooled. Poison information centres could act as a network.LDlow and TDlow in man would then be better and earlier known. The clinicians should, however, then be given better facilities of collaboration with toxicological laboratories, to make it possible to widen the scope of investigations, which now often must be limited to the need of the individual case. Starting from clinical findings animal tests — as is already the practice — should be done to deepen the understanding of mechanisms. Cultures of surviving cells could in some situations add important information and will probably be increasingly used.
Changes in the lipoprotein profile during antihypertensive therapy
Authors: Helgeland Anders , Leren Paul , Kjeldsen Sverre , Eide Ivar , Foss Olav Per 
Published: July 2010

Abstract: In the Oslo study serum lipids have been studied during treatment with some of the most frequently used antihypertensive drugs.Hydrochlorothiazide induced no significant changes. However, those patients with the most marked increase in uric acid showed an increase of serum ti iglycerides. Total cholesterol was unchanged in these men.The β‐adrenoceptorblocking drugs propranolol, aterolol and oxprenolol caused a reduction of HDL cholesterol and an increase of total triglycerides. Tolal cholesterol remained unchanged. Pindolol induced no significant lipoprotein changes.Prazosin reduced total cholesterol and total triglycerides. HDL. cholesterol remained unchanged. LDL + VLDL cholesterol was reduced.
On the occasion of the 40th anniversary of Acta pharmacologica et toxicologica, May 5th, 1985
Authors: Bain James A. 
Published: July 2010

The first issue of Acta pharmacologica et toxicologica was circulated on May 5th, 1945, the very day on which World War II ended in Denmark. The journal is the official publication medium of the Scandinavian Pharmacological Societies. The societies are also represented by associate editors in the editorial board of Pharmacological Reviews. On the happy occasion of the anniversary, we were pleased to receive the following congratulation address from the editor of Pharmacological Reviews, James A. Bain, Ph.D., past president of the International Union of Pharmacology, and Professor of Pharmacology, School of Medicine Emory University, Atlanta, Georgia 30322, U.S.A.Jens S. Schou
Environmental cooling of the newborn pig brain during whole‐body cooling
Authors: Liu Xun , Chakkarapani Ela , Hoque Nicholas , Thoresen Marianne 
Published: July 2010

AbstractAim:  Therapeutic hypothermia after perinatal asphyxia decreases brain injury in newborns, whereas hyperthermia worsens the brain injury. We examined how different clinical practices influence regional brain temperatures during hypothermia.Methods:  Six newborn pigs, which have comparable physiology and brain maturation to human term infants, were maintained at hypothermia (33.5°C) or normothermia with a servo‐controlled whole‐body cooling device that is in clinical use. Pigs were anesthetized and fully instrumented for cardiovascular and temperature (rectal and regional brain) monitoring. Changes in brain temperatures were measured during four different paradigms to mimic different clinical practices.Results:  Inserting an insulating pillow between the head and the heated surface reduced cortex temperature by 1 or 2°C during normothermia (core temperature Tcore 37°C) or hypothermia, Tcore 33.5°C. Reducing ambient temperature from 28°C to 23°C reduced cortex temperature by 3.9 ± 1.9°C. Without a hat and overhead heater at normothermia, cortex and deep brain temperatures were reduced by 1.2 ± 0.8 and 0.7 ± 0.7°C, respectively. Direct overhead heating abolished the normal cortex to deep brain temperature gradient that was maintained if using a head shield.Conclusion:  Brain temperature may differ from core temperature during therapeutic hypothermia influenced by different clinical practices.
Nitric Oxide‐dependent Pigment Migration Induced by Ultraviolet Radiation in Retinal Pigment Cells of the Crab Neohelice granulata
Authors: De Moraes Vaz Batista Filgueira Daza , Guterres Laís Pereira , De Souza Votto Ana Paula , Vargas Marcelo Alves , Boyle Robert Tew , Trindade Gilma Santos , Nery Luiz Eduardo Maia 
Published: July 2010

AbstractThe purpose of this study was to verify the occurrence of pigment dispersion in retinal pigment cells exposed to UVA and UVB radiation, and to investigate the possible participation of a nitric oxide (NO) pathway. Retinal pigment cells from Neohelice granulata were obtained by cellular dissociation. Cells were analyzed for 30 min in the dark (control) and then exposed to 1.1 and 3.3 J cm−2 UVA, 0.07 and 0.9 J cm−2 UVB, 20 nmβ‐PDH (pigment dispersing hormone) or 10 μm SIN‐1 (NO donor). Histological analyses were performed to verify the UV effect in vivo. Cultured cells were exposed to 250 μm L‐NAME (NO synthase blocker) and afterwards were treated with UVA, UVB or β‐PDH. The retinal cells in culture displayed significant pigment dispersion in response to UVA, UVB and β‐PDH. The same responses to UVA and UVB were observed in vivo. SIN‐1 did not induce pigment dispersion in the cell cultures. l‐NAME significantly decreased the pigment dispersion induced by UVA and UVB but not by β‐PDH. All retinal cells showed an immunopositive reaction against neuronal nitric oxide synthases. Therefore, UVA and UVB radiation are capable of inducing pigment dispersion in retinal pigment cells of Neohelice granulata and this dispersion may be nitric oxide synthase dependent.
Routine diagnostic procedures of myelodysplastic syndromes: value of a structural blood cell parameter (NEUT‐X) determined by the Sysmex XE‐2100TM
Authors: LE ROUX G. , VLAD A. , ECLACHE V. , MALANQUIN C. , COLLON J.‐F. , GANTIER M. , SCHILLINGER F. , PELTIER J.‐Y. , SAVIN B. , LETESTU R. , BARAN‐MARSZAK F. , FENAUX P. , AJCHENBAUM‐CYMBALISTA F. 
Published: July 2010

SummaryIntroduction:  Diagnostic features of myelodysplastic syndromes (MDS) are often polymorphic and nonspecific including anemia in most cases. Standard parameters provided by an automated analyzer seldom bring any argument for this diagnosis. The aim of this study was to investigate whether some structural parameters, not routinely provided by SysmexTM XE 2100 analyzer, could help diagnose MDS in a simple way, adapted to routine practice.Methods:  Blood samples from 184 MDS fully annotated cases and 3545 normal blood count controls were performed with XE 2100 SysmexTM analyzer. Quantitative and structural parameters were considered.Results:  We found that the structural neutrophil parameter, NEUT‐X, converted into a semi‐quantitative parameter, the granularity index (GI), could be used as a flag for MDS in front of anemia. Negative GI and anemia were able to make otherwise unrecognized MDS stand out in routine practice, increasing the number of slides addressed to review from 67% to 96%, without leading to a large excess of unfounded slide review among non‐MDS.Conclusion:  Including the GI index in the routine parameters provided by the Sysmex analyzer could be of major help for nonspecialized routine laboratories in detecting MDS.
Mapping the N-Terminal Residues of Epstein-Barr Virus gp42 That Bind gH/gL by Using Fluorescence Polarization and Cell-Based Fusion Assays
Authors: Liu Fengling , Marquardt Gaby , Kirschner Austin N. , Longnecker Richard , Jardetzky Theodore S. 
Published: July 2010

ABSTRACT
Epstein-Barr virus (EBV) requires at a minimum membrane-associated glycoproteins gB, gH, and gL for entry into host cells. B-cell entry additionally requires gp42, which binds to gH/gL and triggers viral entry into B cells. The presence of soluble gp42 inhibits membrane fusion with epithelial cells by forming a stable heterotrimer of gH/gL/gp42. The interaction of gp42 with gH/gL has been previously mapped to residues 36 to 81 at the N-terminal region of gp42. In this study, we further mapped this region to identify essential features for binding to gH/gL by use of synthetic peptides. Data from fluorescence polarization, cell-cell fusion, and viral infection assays demonstrated that 33 residues corresponding to 44 to 61 and 67 to 81 of gp42 were indispensable for maintaining low-nanomolar-concentration gH/gL binding affinity and inhibiting B-cell fusion and epithelial cell fusion as well as viral infection. Overall, specific, large hydrophobic side chain residues of gp42 appeared to provide critical interactions, determining the binding strength. Mutations of these residues also diminished the inhibition of B-cell and epithelial cell fusions as well as EBV infection. A linker region (residues 62 to 66) between two gH/gL binding regions served as an important spacer, but individual amino acids were not critical for gH/gL binding. Probing the binding site of gH/gL and gp42 with gp42 peptides is critical for a better understanding of the interaction of gH/gL with gp42 as well as for the design of novel entry inhibitors of EBV and related human herpesviruses.
Important Role for the Murid Herpesvirus 4 Ribonucleotide Reductase Large Subunit in Host Colonization via the Respiratory Tract
Authors: Gill Michael B. , May Janet S. , Colaco Susanna , Stevenson Philip G. 
Published: July 2010

ABSTRACT

Viral enzymes that process small molecules provide potential chemotherapeutic targets. A key constraint—the replicative potential of spontaneous enzyme mutants—has been hard to define with human gammaherpesviruses because of their narrow species tropisms. Here, we disrupted the murid herpesvirus 4 (MuHV-4) ORF61, which encodes its ribonucleotide reductase (RNR) large subunit. Mutant viruses showed delayed
in vitro
lytic replication, failed to establish infection via the upper respiratory tract, and replicated to only a very limited extent in the lower respiratory tract without reaching lymphoid tissue. RNR could therefore provide a good target for gammaherpesvirus chemotherapy.
Papain-Like Protease 1 from Transmissible Gastroenteritis Virus: Crystal Structure and Enzymatic Activity toward Viral and Cellular Substrates
Authors: Wojdyla Justyna A. , Manolaridis Ioannis , van Kasteren Puck B. , Kikkert Marjolein , Snijder Eric J. , Gorbalenya Alexander E. , Tucker Paul A. 
Published: July 2010

ABSTRACTCoronaviruses encode two classes of cysteine proteases, which have narrow substrate specificities and either a chymotrypsin- or papain-like fold. These enzymes mediate the processing of the two precursor polyproteins of the viral replicase and are also thought to modulate host cell functions to facilitate infection. The papain-like protease 1 (PL1pro) domain is present in nonstructural protein 3 (nsp3) of alphacoronaviruses and subgroup 2a betacoronaviruses. It participates in the proteolytic processing of the N-terminal region of the replicase polyproteins in a manner that varies among different coronaviruses and remains poorly understood. Here we report the first structural and biochemical characterization of a purified coronavirus PL1prodomain, that of transmissible gastroenteritis virus (TGEV). Its tertiary structure is compared with that of severe acute respiratory syndrome (SARS) coronavirus PL2pro, a downstream paralog that is conserved in the nsp3's of all coronaviruses. We identify both conserved and unique structural features likely controlling the interaction of PL1prowith cofactors and substrates, including the tentative mapping of substrate pocket residues. The purified recombinant TGEV PL1prowas shown to cleave a peptide mimicking the cognate nsp2|nsp3 cleavage site. Like its PL2proparalogs from several coronaviruses, TGEV PL1prowas also found to have deubiquitinating activity in anin vitrocleavage assay, implicating it in counteracting ubiquitin-regulated host cell pathways, likely including innate immune responses. In combination with the prior characterization of PL2profrom other alphacoronaviruses, e.g., human coronaviruses 229E and NL63, our results unequivocally establish that these viruses employ two PLpros with overlapping specificities toward both viral and cellular substrates.
A New Cistron in the Murine Hepatitis Virus Replicase Gene
Authors: Stokes Helen L. , Baliji Surendranath , Hui Chang Guo , Sawicki Stanley G. , Baker Susan C. , Siddell Stuart G. 
Published: July 2010

ABSTRACT

We report an RNA-negative, temperature-sensitive (
ts
) mutant of
Murine hepatitis virus
, Bristol
ts
31 (MHV-Br
ts
31), that defines a new complementation group within the MHV replicase gene locus. MHV-Br
ts
31 has near-normal levels of RNA synthesis at the permissive temperature of 33°C but is unable to synthesize viral RNA when the infection is initiated and maintained at the nonpermissive temperature of 39.5°C. Sequence analysis of MHV-Br
ts
31 RNA indicated that a single G-to-A transition at codon 1307 in open reading frame 1a, which results in a replacement of methionine-475 with isoleucine in nonstructural protein 3 (nsp3), was responsible for the
ts
phenotype. This conclusion was confirmed using a vaccinia virus-based reverse genetics system to produce a recombinant virus, Bristol
ts
c31 (MHV-Br
ts
c31), which has the same RNA-negative
ts
phenotype and complementation profile as those of MHV-Br
ts
31. The analysis of protein synthesis in virus-infected cells showed that, at the nonpermissive temperature, MHV-B
rts
c31 was not able to proteolytically process either p150, the precursor polypeptide of the replicase nonstructural proteins nsp4 to nsp10, or the replicase polyprotein pp1ab to produce nsp12. The processing of replicase polyprotein pp1a in the region of nsp1 to nsp3 was not affected. Transmission electron microscopy showed that, compared to revertant virus, the number of double-membrane vesicles in MHV-Br
ts
31-infected cells is reduced at the nonpermissive temperature. These results identify a new cistron in the MHV replicase gene locus and show that nsp3 has an essential role in the assembly of a functional MHV replication-transcription complex.