bluuebunny/crossref_metadata_2025 huggingface dataset:
Liver aldehyde oxidase and xanthine oxidase genetics in the mouse
Authors: Holmes Roger S. , Leijten Lynette R. , Duley John A.
Published: August 2010

A ‘null’ activity variant for the major liver isozyme of aldehyde oxidase (AOX‐1) in adult male mice and an electrophoretically distinct, high activity variant of the second liver isozyme (AOX‐2) were used to examine the segregation of the genetic loci encoding these enzymes (Aox‐1 and Aox‐2 respectively) in breeding studies. A single recombinant between these loci was observed among the 147 backcross progeny examined, which confirms a previous report (Holmes, 1979) for close linkage and genetic distinctness of the two loci. An activity variant for mouse liver xanthine oxidase (XOX) is also reported which behaved as though controlled by codominant alleles at a single locus (designated Xox‐1). Genetic analyses showed that the Xox‐1 locus segregated independently of the multiple‐A ox loci.
‘Malic enzyme’ polymorphism in sheep erythrocytes
Authors: Yaman K. , Tucker E. M.
Published: August 2010

Malic enzyme or malate dehydrogenase (NADP +). E.C.I.I.I.40. catalyses the reaction:

L‐malate + NADP⇄2 pyruvate + CO2+ NADPH

Baker & Manwell (1977), in a survey of a number of different enzymes reported that ‘malic enzyme’ was polymorphic in the erythrocytes and certain other tissues of sheep, and indicated that it would be a potentially useful new genetic marker for this species. This paper confirms the existence of the polymorphism in sheep erythrocytes and presents inheritance and breed data.
The location of structural difference between ovotransferrin types A and B in hens
Authors: Rashid A. M.
Published: August 2010

A comparison of ovotransferrin types A and B showed that in starch gel electrophoresis both types consisted of one major and one minor component. Both types have a similar amino acid composition as do the fragments from each type. Starch gel electrophoresis shows that the cause of the difference in the elec‐trophoretic mobilities between ovotransferrin types A and B lies in the C‐termi‐nal half of the molecule. No physiological difference was found between types A and B, both types donate iron to chicken embryo red cells at equal rate.
Serological and genetic identification of a bovine B lymphocyte alloantigen system
Authors: Newman M. J. , Adams T. E. , Brandon M. R.
Published: August 2010

A two‐colour fluorescence micro cytotoxicity test was used to screen antisera for antibodies specific for bovine B lymphocytes. A total of 114 cattle alloantisera were screened against peripheral blood lymphocytes from 100 unrelated individuals. Anti‐B lymphocyte activity was detected in 47 antisera. Cytotoxic antibodies to antigens other than B lymphocyte specific antigens were removed by absorbing the antisera with buffy coat cells or platelets isolated from whole blood. Selected antisera were used to type paternal half‐sib families. The presence of a polymorphic, MHS‐linked antigen system on B lymphocytes was demonstrated. The tissue distribution and MHS linkage of these antigens suggests this system is analogous to the class II or Ia antigens of other species.
Interaction of the B locus and the GVHR‐selected lines in the graft‐versus‐host reaction in chickens
Authors: Okada Ikuo
Published: August 2010

Genetic differences affecting the degree of splenomegaly in the graft‐versus‐host reaction (GVHR) of chickens were studied. Two B genotypes, B9B9 and B11B11, and two GVHR‐selected lines, H and L, were examined. The degree of splenomegaly of B9 B9→ B11B11 was significantly higher than that of B11B11→ B9B9 for all line combinations. In contrast, the inoculation of H into L gave consistently higher splenomegaly than that of L into H. This suggested that the effects of B locus were higher in hosts than in donors, while those of the GVHR‐selected lines were higher in donors than in hosts.

The analysis of variance revealed that both the differences between the reciprocal combination of B genotypes and between the GVHR line combinations were statistically highly significant. Furthermore, the interaction of B genotypes and GVHR lines was also highly significant.
Correlated responses of chickens to selection for production of antibodies to sheep erythrocytes
Authors: Siegel P. B. , Gross W. B. , Cherry J. A.
Published: August 2010

A bi directional selection experiment was conducted to measure 5‐day antibody titers to sheep erythrocytes in White Leghorn chickens. There was an immediate response to selection with significant differences between lines for the selected trait found in the S1and all subsequent generations. Comparisons of S6, S7and S8generation females revealed differences between lines in disease resistance and in certain reproductive traits such as age at first egg, percentage hen‐day egg production, percentage fertility and duration of fertility. The implications of these correlated responses are important to selection programs for general disease resistance.
Genetic linkage between the loci for phosphohexose isomerase (PHI) and a serum protein (Xk) in horses
Authors: Anderson Leif , Kumar Juneja R. , Sandberg Kaj
Published: August 2010

Genetic linkage between the equine loci for phosphohexose isomerase (PHI) and serum Xk protein was demonstrated by means of segregation data from three sire families. The recombination frequency was estimated from pooled data to be 0.23 ± 0.02; a significant heterogeneity between sires for estimates of the recombination frequency was observed. No indication of linkage was detected between Xk and 14 other blood marker loci. Linkage between the Xk locus and the locus for soluble malic enzyme (ME1) has recently been reported in horses. An equine linkage group designated LG IV comprising the three loci ME1, PH1, and Xk has thus been established. The possibility that the linkage between PH1 and Xk is homologous to the linkage between the loci for PHI and a serum postalbumin (PO‐2) in pigs was discussed.
Breeding for immune responsiveness and disease resistance1
Authors: S. Gavora Jan , Lloyd Spencer J.
Published: August 2010

Animal production efficiency, and product volume and quality can be greatly increased by reducing disease losses. Genetic variation, a prerequisite for successful selection, has been found in animals and poultry exposed to a variety of viral, bacterial and parasitic infections. Breeding for disease resistance can play a significant role alone or in combination with other control measures including disease eradication, vaccination and medication.

Feasibility of simultaneously improving resistance to specific diseases and production traits has been demonstrated. However, selection for specific resistance to all diseases of animals and poultry is impossible. Development of general disease resistance through indirect selection primarily on immune response traits may be the best long‐term strategy but its applicability is presently limited by insufficient understanding of resistance mechanisms. Another hindrance may be negative genetic correlations among various immune response functions: phagocytosis, cell mediated and humoral immunity. To better assess the feasibility of increasing general disease resistance by indirect selection we must obtain estimates of heritability for immune response, disease resistance, and economic production traits, as well as genetic correlations among these traits.

The present level of disease resistance in farm animals resulted from natural selection and from correlated responses to selection for production traits while the influence of artificial selection for resistance was minimal. Future research should be directed towards developing and applying breeding techniques that will increase resistance to diseases without compromising production efficiency and product quailty. This will require cooperation of immunogeneticists, veterinarians and animal and poultry breeders. Significant progress in the improvement of resistance to diseases may result from the application of new techniques of molecular genetics and cell manipulation.
FV blood group and haemoglobin type versus haematological and blood chemical parameters in young Swiss bulls
Authors: Stämpfli G. , P. Ittig H.
Published: August 2010

A relationship between the FV blood group phenotype and 4 out of 45 haematological and blood chemical parameters — red cell number, mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC), and serum iron — has been demonstrated in young bulls of three Swiss cattle breeds. There was also a relationship between haemoglobin type and 7 out of 45 haematological and blood chemical parameters (haemoglobin concentration, red cell number, MCV, MCHC and red cell concentrations of K+ and Na+ and their sum). In addition to expanding the species in which there is an effect of haemoglobin phenotype on MCV to include cattle, these data also demonstrate a significant correlation between their FV phenotype and MCV.
Protein polymorphism in two populations of the wild quail Coturnix coturnix japonica
Authors: Kimura Masao , Oniwa Kiyoko , Ito Shinichi , Isogai Iwahiro
Published: August 2010

To evaluate genetic variability in two populations of the wild quail Cofurnix coturnix japonica, proteins and enzymes were examined by starch gel electrophoresis.

Rare variants so far not observed in domestic quail were found in the following five enzymes; aspartate aminotransferase, acid phosphatase, pancreatic esterase, isocitrate dehydrogenase and lactate dehydrogenase. The proportion of polymorphic loci (Ppoly) and the expected average heterozygosity (H) in one of the two populations were estimated to be 0.484 (15/31) and 0.085, respectively. Those in another population were 0.433 (13/30) and 0.086, respectively. The genetic distance (Nei, 1975) between the two wild quail populations was D= 0.0074. D values of 0.0321 and 0.0189 were estimated between the laboratory quail population previously examined (Kimura et al., 1982) and each of these two wild populations.
Horse haemoglobin phenotyping by agarose gel isoelectric focusing comparison of Thoroughbreds with other Equidae*
Authors: R. Osterhoff D. , Groenewald J.
Published: August 2010

By using isoelectric focusing in thin agarose slab gels 1049 Thoroughbred, 82 Nooit‐gedachter, 45 Percheron and 244 horses of other breeds were examined. The numbers of other Equidae tested were 107 donkeys, 50 mules, 4 common zebras (Equus burchelli boehmi) and 8 mountain zebras (Equus zebra hartmannae). Phenotypic data are presented for all tested animals and gene frequencies are calculated for the horses.
Comparison of ELY‐2.1 with blood group and ELY‐1 markers in the horse*
Authors: Bailey Ernest , Henney Pamela J.
Published: August 2010

The distribution of ELY‐2 was compared to the distribution of blood group factors Aa, Ab, Ac, Ae, Ca, Da, Db, Dc, Dd, De, Df, Dh, Dk, Ka, Pa, Pb, X, Qa, Qc, Ua, and W in 2465 American Standardbred horses and to ELY‐1 in 193 American Standardbred horses. The distribution patterns were different in each case. The segregation of ELY‐2.1 and factors at the A, C, D, K, P, Q, U and T (W) blood group loci and at the ELA locus indicated that ELY‐2.1 is not a product of any of those loci. No segregation data were available for the ELY‐I locus. Family studies indicated that the gene for ELY‐2.1 is not sex‐linked.
Joint Report of the Second International Workshop on Lymphocyte Alloantigens of the Horse, held 3–8 October 1982
Authors: Bailey E. , Antczak D.F. , Bernoco D. , Bull R.W. , Fister R. , Guerin G. , Lázary S. , Matthews S. , McClure J. , Meyer J. , Mottironi V.D. , Templeton J.
Published: August 2010

The Second International Workshop on Lymphocyte Alloantigens of the Horse was held 3–8 October 1982. At this workshop, the 6 specificities identified at the first workshop were confirmed and an additional 5 new specificities were identified and given workshop nomenclature. Four of the new specificities, products of the ELA locus, were named ELA‐W7, W8, W9, and W10. An additional specificity, designated ELY‐2.1, is the product of a locus independent of the ELA locus.

Cell isolation methods were compared at this workshop, Technical variation in methods clearly affected reactivity of many reagents. However, when highly selected reagents were used, antigen assignment did not differ regardless of the cell isolation method. Based on the comparison of methods, isolation procedures in which thrombin was used were more effective than those relying on carbonyl iron or slow centrifugation.
The transfer of bovine J blood group activity to erythrocytes: chemical nature of transferable and of non‐transferable J1
Authors: Wagner R. , Wrenger M. , Oulevey J. , W. Thiele O.
Published: August 2010

The bovine J blood group substance exists as a glycosphingolipid (ceramide deca‐hexoside as well as ceramide dodecahexoside) and as a glycoprotein. The lipidic form occurs in erythrocyte membranes, both forms are found in serum. The lipidic J substances were isolated from erythrocytes and from serum, and identified by thin‐layer chromatography with lipidic J substances isolated from spleen. The glycoprotein nature of the non‐lipidic J of serum was evident by pronase‐catalysed hydrolysis yielding J‐active glycopeptides of lower molecular weights. The lipidic J was completely extracted from lyophilized stroma with chloroform/methanol. From lyophilized serum, however. it was completely extracted only in the presence of water, indicating different binding partners in serum and in erythrocyte membranes.

The J lipid was incorporated as intact molecule into the erythrocyte membrane by a simple incubation technique. The incorporation was inhibited by various glyc‐erophospholipids (called blockers). The J glycoprotein could not be transferred to the erythrocyte membrane.

Three methods are descrjbed which are suitable for the preparation of a blocker‐free fraction enriched with J lipids from J‐positive serum.
The estimation of blood group gene frequencies: a note on the allocation method
Authors: Andersson Leif
Published: August 2010

The principles for estimating gene frequencies in complex blood group systems by the allocation method are discussed. This numerical method is simpler than the maximum likelihood method, but gives the same estimate. It is shown that there are some cases in which the application of a previous description of the method gives incorrect results. The principles are discussed for how family information may be included in the estimation process in order to obtain more precise estimates.
Preliminary report on two new plasma protein polymorphisms in the goose (Anser anser)
Authors: Kuryl Jolanta , Gasparska Jolanta
Published: August 2010

Two‐dimensional agarose gel (pH 8.6)‐horizontal poly acrylamide gel (pH 9.0) electrophoresis of plasma proteins in the goose was done. This method resulted in improved separation of proteins in the pre‐transferrin and transferrin regions. Preliminary evidence was presented for the existence of two new plasma protein poly morphisrns.
Evaluation of linkage between the R‐O‐i and C blood group systems in sheep
Authors: Nguyen T. C.
Published: August 2010

Linkage between the C and I blood group loci in sheep was demonstrated by lod score analysis of data from double backcross matings. The recombination frequency between the I locus and the gene coding for the Cb red cell antigen was estimated to be 0.09 with a standard error of 0.04.
Genetic variation of haemoglobin α‐ and βchains in rabbits detected by iso electric focusing and reversed‐phase chromatography
Authors: Andersson Leif , Bengtsson Sven , Hellman Ulf , Källman Ivan , Ranje Camilla
Published: August 2010

Previous studies on the amino acid sequences and on the amino acid composition of peptides revealed genetic polymorphism both of the haemoglobin α‐chain (Hbα) and β‐chain (Hbβ) in rabbits. In this study, rabbit haemolysates were analysed by isoelectric focusing in a narrow pH range (6.7–7.7) and by reversed‐phase chromatography. Two variants were found for both Hbα and Hbβ. The two methods detected the same variants in this material. Inheritance data were consistent with the hypothesis that the observed Hbα and Hbβ variants were each controlled by two codominant, auto somal alleles. Haemoglobin polymorphism appears to be frequent in domestic rabbits since both variants of each chain were observed in all the three breeds studied.
Preliminary evidence of segregation distortion in the SLA system
Authors: Philipsen Merete , Kristensen Birte
Published: August 2010

The segregation of 11 well‐defined SLA haplotypes was investigated in 40 Land‐race and 48 Large White Danish and Swiss litters. Among the 11 haplotypes, the segregation of one (SLA 20–8.2.11) deviated significantly from the expected 1: 1 segregation ratio in back‐cross families. Tests indicated that these families were homogeneous with respect to segregation distortion, although the distortion was more pronounced in litters sired by heterozygous Danish boars than by heterozygous Swiss boars and Danish and Swiss sows. The data presented do not allow any definite conclusion about the cause of the segregation distortion. The possibility of the distortion being caused either by a complex similar to the T/t‐complex found in mouse and contemplated in man or directly by the SLA region is discussed.
A comparison of bovine lymphocyte antigens
Authors: Stear M. J. , Lyons I. , Dufty J. H. , Nicholas F. W. , Brown S. C.
Published: August 2010

In Canberra, 31 antigens have been described on the surface of bovine lymphocytes. Seven antigens are subgroups of other antigens. Eleven antigens are similar to the eleven antigens which have been described in Melbourne. Fourteen antigens are similar to twelve international‐workshop antigens and two European‐workshop antigens.
Three phenotypes of glucosephosphate isomerase in sheep: improved staining recipe
Authors: Manwell Clyde , Baker C. M. Ann , Graydon Russell J.
Published: August 2010

Contrary to results published recently, we observe three, rather than two, phenotypes for the enzyme glucosephosphate isomerase (EC 5.3.1.9) from sheep. The phenotypic electro phoretic patterns conform to the patterns observed for this dimeric enzyme in other species. Genotype frequencies in a flock of South downs do not deviate significantly from those predicted under the assumption of the Hardy‐Weinberg equilibrium. A remarkable observation is that the electro phoretically distinct phenotypes of GPI are largely or entirely obliterated by the addition of 1–10 mmol/1 MgCl2 to the electro phoretic buffers. Modification of the usual staining recipe for GPI result in greater resolution and shorter staining times.
Association of the M blood group system with bovine mastitis*
Authors: Larsen B. , Jensen N.E. , Madsen P. , Nielsen S.M. , Klastrup O. , Madsen P.S.
Published: August 2010

Associations of the 11 bovine blood group systems with mastitis were examined in Red Danish dairy cattle. The mastitis status was followed during three lactational periods. A significant effect of the M blood group system on mastitis incidence was observed in the first and second lactation periods and a lower frequency of mastitis is found among animals lacking the M' factor as compared to those having the M' blood group factor. The significance of these results are discussed in view of the close relation between the M blood group system and the bovine lymphocyte antigens (BoLA), and the expected effect of eliminating the M' gene from the breed is estimated.

Among the remaining 10 blood group systems, the T' system was the only system showing an overall effect on mastitis, and only in first and third lactation. However, the T' system was inconsistent with regard to the effect of the T' gene on the various mastitis diagnoses.
Evaluation of partial β‐adrenoceptor agonist activity
Authors: Lipworth Brian J. , Grove Alison
Published: August 2010

A partial β‐adrenoceptor (β‐AR) agonist will exhibit opposite agonist and antagonist activity depending on the prevailing degree of adrenergic tone or the presence of a β‐AR agonist with higher intrinsic activity. In vivo partial β‐AR agonist activity will be evident at rest with low endogenous adrenergic tone, as for example with chronotropicity (β1/β2), inotropicity (β1) or peripheral vasodilatation and finger tremor (β2). β‐AR blocking drugs which have partial agonist activity may exhibit a better therapeutic profile when used for hypertension because of maintained cardiac output without increased systemic vascular resistance, along with an improved lipid profile. In the presence of raised endogenous adrenergic tone such as exercise or an exogenous full agonist, β‐AR subtype antagonist activity will become evident in terms of effects on exercise induced heart rate (β1) and potassium (β2) responses. Reduction of exercise heart rate will occur to a lesser degree in the case of a β‐adrenoceptor blocker with partial β1‐AR agonist activity compared with a β‐adrenoceptor blocker devoid of partial agonist activity. This may result in reduced therapeutic efficacy in the treatment of angina on effort when using β‐AR blocking drugs with partial β1‐AR agonist activity. Effects on exercise hyperkalaemia are determined by the balance between β2‐AR partial agonist activity and endogenous adrenergic activity. For predominantly β2‐AR agonists such as salmeterol and salbutamol, potentiation of exercise hyperkalaemia occurs. For predominantly β2‐AR antagonists such as carteolol, either potentiation or attenuation of exercise hyperkalaemia occurs at low and high doses respectively. β2‐AR partial agonist activity may also be expressed as antagonism in the presence of an exogenous full agonist, as for example attenuation of fenoterol induced responses by salmeterol. Studies are required to investigate whether this phenomenon is relevant in the setting of acute severe asthma.
Effects of lanreotide, a somatostatin analogue, on postprandial gastric functions and biliopancreatic secretions in humans
Authors: Lamrani A. , Vidon N. , Sogni P. , Nepveux P. , Catus F. , Blumberg J. , Chaussade S.
Published: August 2010

Aims Lanreotide is a novel synthetic somatostatin analogue. A long‐acting formulation of lanreotide has been shown to be effective for the treatment of gastroentero‐pancreatic hormone‐producing tumours but effects on postprandial digestive and absorptive functions remain obscure. The aim of the present study was to evaluate the effects of intravenous lanreotide on gastric and biliopancreatic secretions in man as well as the absorption of nutrients and the duodeno‐caecal transit time after ingestion of an homogenized meal (500 kcal, 55% carbohydrates, 15% proteins, 30% lipids).

Methods Eight healthy male volunteers were studied on two occasions within a 2 weeks interval, using a perfusion method. They received in single‐blind and random order continuous i.v. infusion of either placebo or lanreotide (100 μg h−1 after a bolus of 100 μg 15 min before the beginning of the study).

Results Lanreotide significantly decreased gastric acid secretion (90%) for the initial 3 h period. Gastric emptying was not significantly molfied by lanreotide infusion. Compared with placebo, lanreotide almost completely abolished both bile salts and lipase responses to the meal. It largely increased the duodeno‐caecal transit time and decreased significantly the duodenal absorption of carbohydrates and triglycerides.

Conclusions Since lanreotide has powerful effects on gastrointestinal functions, it could be useful in the prevention or in the treatment of pancreatic and bowel fistulas as well as short bowel syndrome.
Effect of Anapsos (Polypodium leucotomos extract) on in vitro production of cytokines
Authors: Sempere J. M. , Rodrigo C. , Campos A. , Villalba J. F. , Diaz J.
Published: August 2010

Aims The aim of the study was to test the immunomodulating capacity of Anapsos, Polypodium leucotomos extract, in vitro in an attempt to explore how this extract acts from an immunological point of view and thus to identify a common link capable of explaining most of its effects.

Methods Polypodium leucotomos rhizomes were harvested in Guatemala and the extract, Anapsos, obtained. Mononuclear cells were obtained by density gradent centrifugation from healthy donors, and stimulated with phytohemagglutinin or Pokeweed with and without Anapsos and with Anapsos alone. Cell proliferation was determined by thymidine incorporation. Cells were also stimulated and the following cytokines determined by ELISA at 0, 12, 24, 48, 72, and 96 h: IL‐lP, TNF‐a, IL‐2, INF‐8, IL‐4 and IL‐10.

Results Anapsos, Polyodium leucotomos extract, has a modulating effect on the in vitro production and release of cytoknies by peripheral blood mononuclear cells of healthy subjects. At doses effective in vivo, Anapsos can stimulate PBMNc proliferation, delay IL‐1β secretion and at the same time increase that of IL‐2, IL‐10, and INF‐γ.

Conclusions Anapsos may have an antagonistic effect on some of the cytokines released on cell stimulation with LPS and/or PHA, which suggests that this product has a pleiotropic effect on different populations in the immune system.
Development of prescribing indicators for elderly medical inpatients
Authors: Oborne C. Alice , Batty Gwenno M. , Maskrey Vivienne , Swift C. G. , Jackson S. H. D.
Published: August 2010

Aims To identie and improve suboptimal prescribing for elderly patients we have developed a number of prescribing indicators which focus on areas of concern and allow evaluation of the benefit of interventions. We report here on fourteen indcators. Methods The indicators are of three types: a) purely descriptive with no attempt to define optimal values, e.g. number of items prescribed per patient; b) based on unnecessary or potentially harmful prescribing, e.g. duplication; c) assessing the appropriateness of prescribing specific drugs or combinations e.g. digoxin and warfarin/aspirin in atrial fibrillation (AF). Appropriateness was defined on the basis of objective research findings and involved comparing individual patient clinical records to criteria for appropriate prescribing. Prescribing and personal data were collected for medical inpatients aged 65 years or over in 19 hospitals in England and Wales. A total of 1686 patients were included, median age 81 years, 41% were male. Results Patients were prescribed 11 475 items, mean 4.6 regular items per patient. Completion of drug allergy/sensitivity statements varied from 3 to 93% between units. Use of generic name and specification of a maximum frequency of administration for‘as required’medicines were more consistent, ranging from 76–94% and 52–81% respectively. Little duplication of therapy was seen. Benzohazepines were prescribed for 22% patients, but were appropriate in only approximately one third of these. Of the 2% patients prescribed an angiotensin convecting enzyme inhibitor with a potassium‐sparing diuretic or potassium supplement, prescription of the combination was appropriate in 84%. Coprescription of steroids with β2‐adrenoceptor agonists appeared excessive in 67% patients receiving a β2‐adrenoceptor agonist, as only 51% had documented evidence of steroid responsiveness or another indication for steroids. Stroke prophylaxis in AF was inadequate: 22% patients prescribed digoxin also received warfarin or aspirin 300 mg whereas 64% should have received the coprescription.

Conclusions These prescribing indicators are sensitive to inappropriate prescribing for elderly medical inpatients and cover a wide range of therapeutic areas. They should enable changes in prescribing quality to be measured objectively. Interhospital variation in casemix resulted in substantial differences in the proportion of patients in whom it would have been appropriate to prescribe specific drugs or combinations and prevented derivation of reference ranges of optimal prescribing for four indicators.
Renal excretion and pharmacokinetics of foscarnet in HIV sero‐positive patients: effect of probenecid pretreatment
Authors: Noonnohamed F. H. , Youle M. S. , Higgs C. J. , Gazzard B. G. , Lant A. F.
Published: August 2010

Aims The present study was undertaken to test whether the anti‐viral agent foscarnet undergoes sipficant tubular secretion, by using probenecid, an inhibitor of the organic acid secretory pathway in the proximal segment of the nephron.

Methods The pharmacokinetics and renal excretion of foscarnet (90 mg kg−1 infused over 2 h) have been investigated, in the absence and presence of probenecid pretreatment (1 g twice daily for 3 days) in a group of 10 HIV seropositive patients. Results Mean (± s.d.) peak plasma concentrations were 904 ± 65 μm (foscarnet) and 862 ± 97 μm (foscarnet + probenecid) whilst the plasma AUC values were 3326 ± 451 μm h and 3133 ± 476 μm h respectively. Terminal elimination half‐life remained unchanged at 5.6 ± 0.7 h and the respective volumes of distribution at steady state were 23 ± 31 (foscamet) and 25 ± 31 (foscamet + probenecid). Mean total body clearance was 110 ± 17 ml min−1 (foscarnet) and 113 ± 13 ml min−1 (foscarnet + probenecid) and the corresponding renal clearances of foscarnet were 102 ± 5 ml min−1 and 105 ± 5 ml min−1 respectively. There were no significant differences in the total amount of foscarnet excreted by the kidney with 95 ± 5% (foscarnet) and 91± 6% (foscarnet + probenecid) of the intravenous dose excreted within 24 h. Glomerular filtration rates at 109 ± 12 ml min−1 (foscarnet) and 100 ± 13 ml min−1 (foscarnet + probenecid) and respective creatinine clearances at 120 ±15 and 119 ± 10 ml min−1 remained unchanged throughout the study.

Conclusion The study shows that foscarnet is not transported via the probenecid‐sensitive organic acid secretory pathway in the proximal tubule; the renal elimination of foscarnet is via glomerular filtration.
The effect of intravenous aminophylline on essential tremor
Authors: Buss D. C. , Marshall R. W. , Milligan N. , McQueen I. , Compston D. A. S. , Routledge P. A.
Published: August 2010

Aims The effects of intravenous aminophylline (375 mg) or placebo (saline) were studied in 10 patients with benign essential tremor.

Methods This was a single‐blind crossover study. Patients received aminophylline by i.v. infusion over 15 min or sahne at least 1 week apart. Tremor was measured by a peizoresistive accelerometer at 15 min intervals predose and up to 2 h. Plasma theophylline concentrations were measured by h.p.1.c.

Results Tremor power was significantly greater following aminophylline (5.67–6.2 Hz) than placebo (5.6–5.9 Hz).

Conclusions We conclude that intravenous aminophylline potentiates benign essential tremor when given acutely by the intravenous route in the doses required to achieve therapeutic benefits in asthma.
Therapeutic drug monitoring in a developing country: an overview
Authors: Gogtay N. J. , Kshirsagar N. A. , Dalvi S. S.
Published: August 2010

Therapeutic Drug Monitoring (TDM) was introduced in India in the mid and late 1980s and the last 10 years have seen it grow, together with the growth of separate Clinical Pharmacology departments. The TDM service in the country is broadly of two types: in large teaching hospitals where the service is available through departments of Clinical Pharmacology, and in the private sector, where drug estimations are done by clinical biochemistry departments with minimal interpretation. This article is based on literature review and our own experiences over a 10 year period in a department of Clinical Pharmacology. It focuses on the evolution of TDM, its problems such as lack of funding, special aspects such as the impact of ethnic diff;erences, nutritional defi;ciencies, quality of medicines and availability of generic products; its utility as a research tool and its future.
Therapeutic drug monitoring: antiarrhythmic drugs
Authors: Campbell T. J. , Williams K. M.
Published: August 2010

Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast‐inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the b‐adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents.
Physiologically based pharmacokinetic modelling of the three‐step metabolism of pyrimidine using13C‐uracil as anin vivoprobe
Authors: Ito Suminobu , Kawamura Takeshi , Inada Makoto , Inoue Yoshiharu , Hirao Yukihiro , Koga Toshihisa , Kunizaki Jun‐ichi , Shimizu Takefumi , Sato Hitoshi
Published: August 2010

Aims

Approximately 80% of uracil is excreted as β‐alanine, ammonia and CO2via three sequential reactions. The activity of the first enzyme in this scheme, dihydropyrimidine dehydrogenase (DPD), is reported to be the key determinant of the cytotoxicity and side‐effects of 5‐fluorouracil. The aim of the present study was to re‐evaluate the pharmacokinetics of uracil and its metabolites using a sensitive assay and based on a newly developed, physiologically based pharmacokinetic (PBPK) model.

Methods

[2–13C]Uracil was orally administrated to 12 healthy males at escalating doses of 50, 100 and 200 mg, and the concentrations of [2–13C]uracil, [2–13C]5,6‐dihydrouracil and β‐ureidopropionic acid (ureido‐13C) in plasma and urine and13CO2in breath were measured by liquid chromatography–tandem mass spectrometry and gas chromatograph–isotope ratio mass spectrometry, respectively.

Results

The pharmacokinetics of [2–13C]uracil were nonlinear. The elimination half‐life of [2–13C]5,6‐dihydrouracil was 0.9–1.4 h, whereas that of [2–13C]uracil was 0.2–0.3 h. The AUC of [2–13C]5,6‐dihydrouracil was 1.9–3.1 times greater than that of [2–13C]uracil, whereas that of ureido‐13C was 0.13–0.23 times smaller. The pharamacokinetics of13CO2in expired air were linear and the recovery of13CO2was approximately 80% of the dose. The renal clearance of [2–13C]uracil was negligible.

Conclusion

A PBPK model to describe13CO2exhalation after orally administered [2–13C]uracil was successfully developed. Using [2–13C]uracil as a probe, this model could be useful in identifying DPD‐deficient patients at risk of 5‐fuorouracil toxicity.
Effects of grapefruit juice on the pharmacokinetics of acebutolol
Authors: Lilja Jari J. , Raaska Kari , Neuvonen Pertti J.
Published: August 2010

Aims

We aimed to investigate effects of grapefruit juice on acebutolol pharmacokinetics.

Methods

In a randomized cross‐over study, 10 healthy subjects ingested 200 mL grapefruit juice or water three times daily for 3 days and twice on day 4. On day 3, each subject ingested 400 mg acebutolol with grapefruit juice or water. The concentrations of acebutolol and its metabolite diacetolol were measured in plasma and urine up to 33 h.

Results

Grapefruit juice decreased the peak plasma concentration (Cmax) of acebutolol by 19% from 872 ± 207 ng mL−1to 706 ± 140 ng mL−1(95% CI on the difference −306, −26.4;P < 0.05), and the area under the concentration time curve (AUC0−33 h) by 7%, from 4498 ± 939 ng mL−1 h to 4182 ± 915 ng mL−1h (95% CI −609, −23.0;P < 0.05). The half‐life (t1/2) of acebutolol prolonged from 4.0 to 5.1 h (P < 0.05). The time to peak concentration and the amount of acebutolol excreted into urine (Ae) were unchanged. TheCmax, AUC0−33 h, and Ae of diacetolol were decreased by 24% (P < 0.05), 18% (P < 0.05), and 20% (P < 0.01), respectively, by grapefruit juice.

Conclusion

Grapefruit juice caused a small decrease in the plasma concentrations of acebutolol and diacetolol by interfering with gastrointestinal absorption. The interaction between the grapefruit juice and acebutolol is unlikely to be of clinical significance in most of the patients.
Lupin allergy: a hidden killer in the home
Authors: Sanz M. L. , De Las Marinas M. D. , Fernández J. , Gamboa P. M.
Published: August 2010

This review addresses the problem of lupin sensitization in the home environment. We summarize the data currently available on allergy to lupin, which has become, in recent years, a hidden killer in our homes. Since 2006, when lupin was included in European regulations as a food whose presence must be declared, the situation may have changed. Nevertheless, we must take into account the possibility of undeclared allergenic ingredients or the presence of ‘hidden’ allergens, given that contamination during food production processes may be a great risk for sensitized individuals. Furthermore, the United States, Japan, Australia and New Zealand still do not include lupin among the ingredients that must be listed on foodstuff labelling. Our responsibility is to educate the public so that they are aware of the danger and look for lupin in the labels of products that run the risk of containing it. Lupin allergy can manifest itself in isolation or in parallel to peanut allergy. Identification of the proteins causing possible cross‐reactivity is complicated, and new structural studies are needed. To date, it has not been possible to clearly identify the allergens responsible for isolated lupin sensitization in relation to parallel and/or cross‐sensitization between lupin and peanut. Most of the allergenic proteins of lupin are α‐ and β‐conglutins, with a lesser presence of γ‐ and δ‐conglutins. A β‐conglutin corresponding to Lup an 1, with a sequence similar to Ara h 1, has been identified as a major allergen of lupin in patients with allergy following lupin ingestion.

Cite this as: M. L. Sanz, M. D. de las Marinas, J. Fernández and P. M. Gamboa, Clinical & Experimental Allergy, 2010 (40) 1461–1466.
Oral and systemic administration of β-glucan protects against lipopolysaccharide-induced shock and organ injury in rats
Authors: Sandvik A , Wang Y Y , Morton H C , Aasen A O , Wang J E , Johansen F-E
Published: August 2010

β-Glucans are glucose polymers with a variety of stimulatory effects on the immune system. The objective of this study was to determine the effect of prophylactic oral administration of soluble Saccharomyces cerevisiae-derived β-1,3/1,6-glucan (SBG) on the outcome of experimental endotoxaemia and shock-associated organ injury. Male Wistar rats were pretreated with SBG orally (SBGpo, 20 mg/kg/day) for 14 days, subcutaneously (SBGsc, 2 mg/kg/day) for 3 days, or vehicle (placebo). Rats were anaesthetized and subjected to endotoxaemia by intravenous infusion of Escherichia coli lipopolysaccharide (LPS) (6 mg/kg) or saline infusion (sham). We observed significant levels of plasma β-glucan in the SBGpo group (P < 0·5), although the SBGsc group had levels approximately 40-fold higher despite a 10-fold lower dose. SBG prophylaxis caused enhanced blood pressure recovery following LPS-induced blood pressure collapse. Oral treatment with SBG attenuated the LPS-induced rise in plasma creatinine levels (P < 0·05), indicating protection against renal injury. SBG also attenuated the plasma levels of aspartate aminotransferase and alanine aminotransferase (SBGpo, P < 0·01; SBGsc, P < 0·01), indicating protection against LPS-induced hepatic injury. A moderate increase in baseline interleukin (IL)-1β levels was observed in the SBGsc group (P < 0·05). In the LPS-challenged rats, plasma levels of proinflammatory cytokines was moderately reduced in both SBG-treated groups compared to placebo. SBG treatment, particularly oral administration, had a striking effect on the haemodynamics of LPS-treated rats, although only a minute fraction of the orally administered β-glucan translocated to the circulation. Enhanced organ perfusion may thus be responsible for the attenuated levels of indicators of kidney and liver injury seen in SBG-treated rats.
‘Danger’ effect of low-density lipoprotein (LDL) and oxidized LDL on human immature dendritic cells
Authors: Zaguri R , Verbovetski I , Atallah M , Trahtemberg U , Krispin A , Nahari E , Leitersdorf E , Mevorach D
Published: August 2010

Dendritic cell (DC) maturation may accelerate autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, and may contribute to accelerated atherosclerosis seen in these patients. The immune system responds to both exogenous and endogenous ‘dangerous’ signals that can induce dendritic cell maturation. We have found that autologous plasma contains danger signals that induce up-regulation of major histocompatibility complex (MHC) class II and co-stimulatory molecules in immature DCs (iDCs). The objective of this study was to determine whether low-density lipoprotein (LDL) and/or oxidized LDL (oxLDL) constitute danger signals, and to assess the effect of exposure to LDL and oxLDL following monocyte differentiation into iDCs in lipoprotein-deficient serum (LPDS). IDCs were generated in the presence of autologous plasma or LPDS. Expression of maturation and migration molecules was evaluated using flow cytometry, and morphology was assessed by light microscopy. Pro- or anti-apoptotic effect was determined using annexin V and propidium iodide binding. Phagocytosis of apoptotic cells was evaluated using autologous plasma or LPDS. LDL and oxLDL were clearly able to slightly up-regulate levels of HLA-DR and co-stimulatory molecule CD86. High oxLDL concentrations (50–100 µg/ml) were associated with expression of additional maturation molecules. Moreover, iDCs that were prepared in LPDS showed partial maturation following exposure to LDL and oxLDL, and improved tolerogenic apoptotic cell uptake. This study suggests that oxLDL, and to some extent LDL, are at least partly responsible for the iDC ‘danger’ response induced by autologous plasma.
The chemokine network. II. On how polymorphisms and alternative splicing increase the number of molecular species and configure intricate patterns of disease susceptibility
Authors: Colobran R , Pujol-Borrell R , Armengol M P , Juan M
Published: August 2010

In this second review on chemokines, we focus on the polymorphisms and alternative splicings and on their consequences in disease. Because chemokines are key mediators in the pathogenesis of inflammatory, autoimmune, vascular and neoplastic disorders, a large number of studies attempting to relate particular polymorphisms of chemokines to given diseases have already been conducted, sometimes with contradictory results. Reviewing the published data, it becomes evident that some chemokine genes that are polymorphic have alleles that are found repeatedly, associated with disease of different aetiologies but sharing some aspects of pathogenesis. Among CXC chemokines, single nucleotide polymorphisms (SNPs) in the CXCL8 and CXCL12 genes stand out, as they have alleles associated with many diseases such as asthma and human immunodeficiency virus (HIV), respectively. Of CC chemokines, the stronger associations occur among alleles from SNPs in CCL2 and CCL5 genes and a number of inflammatory conditions. To understand how chemokines contribute to disease it is also necessary to take into account all the isoforms resulting from differential splicing. The first part of this review deals with polymorphisms and the second with the diversity of molecular species derived from each chemokine gene due to alternative splicing phenomena. The number of molecular species and the level of expression of each of them for every chemokine and for each functionally related group of chemokines reaches a complexity that requires new modelling algorithms akin to those proposed in systems biology approaches.
Amino sugars in fungal melanins and soil humic acids
Authors: COELHO R. R. R. , SACRAMENTO D. R. , LINHARES L. F.
Published: August 2010

Humic acids from six Brazilian topsoils (three Latosols and three Podzols) and five soil fungal melanins were hydrolysed and the released amino sugars qualitatively and quantitatively determined by capillary gas‐liquid chromatography. Melanins were obtained from liquid culture media, synthesized with nitrate or asparagine as a source of N, of Stachybotrys atra, Aspergillus glaucus, Eurotium echinulatum and Hendersonula toruloidea. Glucosamine (48–60%), galactosamine (39–52%), and traces of mannosamine were detected in all humic acids. The total amino sugar content ranged from 1351 to 2287 mg kg−1. In the fungal melanins analysed, mostly glucosamine (80–99%) and trace to small amounts of galactosamine and mannosamine (<10%) were found in amounts ranging from 192 to 635 mg kg−1. The Occurrence of mannosamine in fungal melanins and fungal polysaccharides had not previously been found. The present study gives additional data to the theory that fungal melanins may play a role, as precursors, in the formation of soil organic matter.
Soil and human health: a review
Authors: OLIVER M. A.
Published: August 2010

Soil can affect human health in several ways leading either to specific diseases or to more general ill health. Some illnesses are caused by people's eating soil (geophagia), or by their inhaling it which can lead to malignancy if the soil contains asbestiform minerals; pathogens in the soil can lead to tetanus and infestations of hookworm, and particles may enter the body through abrasions and cause a form of elephantiasis. Radon from the soil is implicated in some cancers, and poorly drained soil has been linked recently with infant mortality. Most examples of ill health associated with the soil are caused by concentrations of elements in food or water that are either deficient or toxic. These elements include aluminium, arsenic, cadmium, copper, fluorine, iodine, lead, selenium, thallium and zinc. Their concentrations might reflect the natural condition of the soil, or the effects of people's actions, such as pollution. In isolated subsistence communities that grow their own food, distinct relations between elements and the aetiology of diseases can be identified. Examples include Keshan disease caused by selenium deficiency, and itai‐itai disease caused by excess cadmium. Some of the relations between soil and health are uncertain and the causes putative, and they require further research to validate them. They include the association of heart disease with poor acid soil, as in the glaciated regions of northern Europe and the coastal plain of the eastern United States of America. Even for well‐defined relations it is evident that many are more complex than was originally thought, however, and greater understanding will require multidisciplinary investigation.