Impact of the Recent Measurements of the Top-Quark and W-Boson Masses on Electroweak Precision Fits.

We assess the impact of the very recent measurement of the top-quark mass by the CMS Collaboration on the fit of electroweak data in the standard model and beyond, with particular emphasis on the prediction for the mass of the W boson. We then compare this prediction with the average of the corresponding experimental measurements including the new measurement by the CDF Collaboration, and discuss its compatibility in the standard model, in new physics models with oblique corrections, and in the dimension-six standard model effective field theory. Finally, we present the updated global fit to electroweak precision data in these models.

Influence of Si addition on the microstructure and mechanical properties of Ti-35Nb alloy for applications in orthopedic implants.

In the development of new materials for orthopedic implants, special attention has been given to Ti alloys that show biocompatible alloy elements and that are capable of reducing the elastic modulus. Accordingly, Ti-Nb-Si alloys show great potential for application. Thus, this is a study on the microstructures and properties of Ti-35Nb-xSi alloys (x=0, 0.15, 0.35 and 0.55) (wt%) which were thermally treated and cooled under the following conditions: furnace cooling (FC), air cooling (AC), and water quenching (WQ). The results showed that Si addition is effective to reduce the density of omega precipitates making beta more stable, and to produce grain refinement. Silicides, referred as (Ti,Nb)3Si, were formed for alloys containing 0.55% Si, and its formation presumably occurred during the heating at 1000°C. In all cooling conditions, the hardness values increased with the increasing of Si content, as a result from the strong Si solid solution strengthening effect, while the elastic modulus underwent a continuous reduction due to the reduction of omega precipitates in beta matrix. Lower elastic moduli were observed in water-quenched alloys, which concentration of 0.15% Si was more effective in their reduction, with value around 65 GPa. Regarding Ti-35Nb-xSi alloys (x=0, 0.15 and 0.35), the "double yield point" phenomenon, which is typical of alloys with shape memory effect, was observed. The increase in Si concentration also produced an increase from 382 MPa to 540 MPa in the alloys' mechanical strength. Ti-35Nb-0.55Si alloy, however, showed brittle mechanical behavior which was related to the presence of silicides at the grain boundary.

Differential cytogenetic profile in advanced chronic myeloid leukemia with sequential lymphoblastic and myeloblastic blast crisis.

Frequency of additional chromosomal abnormalities in chronic myeloid leukemia (CML) is estimated to be 7% in chronic phase and increases to 40-70% in advanced disease. Progression of CML from chronic phase to accelerated phase or blast crisis is often associated with secondary chromosomal aberrations. We report an exceptional case of CML as debut in lymphoblastic blast crisis and a subsequent progression in myeloblastic blast crisis with rare cytogenetic abnormalities.

Nutritional impact on health and performance in intensively reared rabbits.

The present work summarizes research related to the definition of nutrient recommendations for feeds used in the intensive production of rabbit's meat. Fibre is the main chemical constituent of rabbit diets that typically contain 320 to 360 and 50 to 90 g/kg of insoluble and soluble fibre, respectively. Instead, the dietary contents of cereal grains (~120 to 160 g/kg), fat (15 to 25 g/kg) and protein concentrates (150 to 180 g/kg) are usually low with respect to other intensively reared monogastric animals. Cell wall constituents are not well digested in rabbits, but this effect is compensated by its stimulus of gut motility, which leads to an increasing rate of passage of digesta, and allows achieving an elevated dry matter intake. A high feed consumption and an adequate balance in essential nutrients are required to sustain the elevated needs of high-productive rabbits measured either as reproductive yield, milk production or growth rate in the fattening period. Around weaning, pathologies occur in a context of incomplete development of the digestive physiology of young rabbits. The supply of balanced diets has also been related to the prevention of disorders by means of three mechanisms: (i) promoting a lower retention time of the digesta in the digestive tract through feeding fibre sources with optimal chemical and physical characteristics, (ii) restricting feed intake after weaning or (iii) causing a lower flow of easily available substrates into the fermentative area by modifying feed composition (e.g. by lowering protein and starch contents, increasing its digestibility or partially substituting insoluble with soluble fibre), or by delaying age at weaning. The alteration in the gut microbiota composition has been postulated as the possible primary cause of these pathologies.

Effect on digestion and performance of dietary protein content and of increased substitution of lucerne hay with soya-bean protein concentrate in starter diets for young rabbits.

The aim of this work was to study the effect of protein source / availability on the intestinal microbiota, digestive traits and nutritional performance of early-weaned rabbits. The effects of supplemental antibiotics in the drinking water were also evaluated. Four isoenergetic and isofibrous diets were formulated: a control diet with a high protein (207 g/kg dry matter (DM)) and lucerne hay content (HPHL), a diet with low crude protein (CP) (179 g/kg DM) and high lucerne hay content (LPHL) and low protein diets in which the lucerne hay in diet LPHL was replaced partially (LPML) or totally (LPLL) with soya-bean protein concentrate. Rabbits, weaned at 25 days (52 per diet), were fed the experimental diets for a 2-week period and thereafter received a commercial diet until 56 days of age. The incidence of mortality was investigated using 70 animals per diet without supplemental medication. The profile of the ileal microbiota was studied at 35 days of age in rabbits treated (18 per diet) or not (12 per diet) with antibiotic. As expected, supplementation with antibiotics effectively reduced fattening mortality rate and microbial biodiversity. However, lowering of also the dietary CP content led to a reduction in the mortality rate ( P < 0.05), both in animals treated with (by 80%) or without (by 39%) antibiotics. In addition, there was a reduction ( P < 0.05) in the frequency of Clostridium perfringens in non-medicated animals. Neither jejunal morphology nor growth performance, over the whole fattening period, was affected by dietary CP content of the experimental diets. However, with HPHL, feed efficiency was higher (by 4.8%; P < 0.01) than with LPHL diets. Substitution of lucerne hay with soya-bean meal in low protein diets did not affect apparent faecal or ileal digestibility of DM and CP. However, the ileal digestibility of cystine, alanine, aspartic acid, and proline was lowered ( P < 0.05) with increasing substitution by soya bean. Nevertheless, ileal CP flow, incidence of mortality and presence of C. perfringens were unaffected. Our results suggest that a reduction in dietary CP, resulting in reduced lumenal flows of nitrogen through the ileum, may be beneficial for young rabbits and limit the numbers of potentially harmful bacteria in the lower gut. Modulation of dietary CP should be contemplated as a strategy to increase the intestinal health in rabbits.

Effect of substitution of a soybean hull and grape seed meal mixture for traditional fiber sources on digestion and performance of growing rabbits and lactating does.

The aim of this work was to determine what concentration of a mixture of soybean hulls and defatted grape seed meal (SHDG) could be included in diets that meet or exceed ADL and particle size requirements for rabbits. Four isonitrogenous and isofibrous pelleted diets were formulated, with similar ADL concentration and particle size (18.3% CP, 42.6% NDF, 7.1% ADL, and 34.9% of particles larger than 0.315 mm, on a DM basis). Diets contained a constant ratio of soybean hulls:defatted grape seed meal (81:19) provided at 0, 13.3, 26.7, or 40% SHDG, which was substituted for a 35:35:30 mixture of alfalfa hay, sunflower hulls, and wheat straw. Thirty-six rabbits were used to determine nutrient digestibility and cecotrophy traits. A feeding trial was carried out using 160 weanling rabbits (30 d of age; 536 +/- 7.1 g). Milk production was measured in 56 rabbit does. Increasing concentrations of SHDG in the diet did not affect digestibilities of DM, GE, or NDF or DE that were on average 54.7, 55.2, and 21.6% and 10.2 MJ/kg of DM, respectively. Digestibility of CP decreased in diets containing 40% (P = 0.002) and 26.7% (P = 0.054) SHDG compared with diets containing a lower percent of SHDG. Daily recycling of CP through cecotrophy, an indicator of microbial protein production, was not affected by SHDG inclusion. Growing rabbits fed 40% SHDG had reduced ADFI and ADG compared with rabbits fed 26.7% SHDG or less (106 vs. 113, 111, or 111 g/d, and 35.8 vs. 37.8, 36.6, or 37.6 g/d, respectively). There was no effect on G:F from adding SHDG to the diets. In the 2-wk period after weaning, ADG decreased (P = 0.031) for rabbits fed 40% SHDG compared with rabbits fed 26.7% SHDG or less (28.4 vs. 32.2, 30.8, of 32.2 g/d), with no effect on ADFI or G:F. Type of diet did not influence mortality during the fattening period, which averaged 6.25%. Rabbit does fed 40% SHDG had reduced ADFI (411 vs. 430 g/d; P = 0.023) compared with rabbits fed 26.7% SHDG or less, with no effect (P > 0.11) on milk production, weight of the litter at 21 d and at weaning (30 d), or parturition-effective mating interval. In conclusion, SHDG can be included up to 26.7% in diets for fattening rabbits and lactating does that meet ADL and particle size requirements.

Evaluation of readmissions in hematopoietic stem cell transplant recipients.

BACKGROUND: There is a lack of information on health expenses caused by readmissions among hematopoietic stem cell transplant (HSCT) recipients. We analyzed the rate, causes, and evolution of hospitalization after HSCT. METHODS: We retrospectively studied 140 consecutive patients who received an autologous HSCT (n = 107; 76.4%) or an allogeneic HSCT (n = 33; 23.6%) in our institution from May 2001 through September 2004. RESULTS: There were 45 readmissions in 28 patients (20%): three (10%) in the autologous and 25 (90%), in the allogeneic HSCT cohorts. The overall median age was 35.3 +/- 13.5 years and 54% were women. Hematologic diseases were: multiple myeloma (n = 1, 4%), myelodysplastic syndrome (n = 2, 7%), acute lymphoblastic leukemia (n = 2, 7%), aplastic anemia (n = 2, 7%), chronic myeloid leukemia (n = 3, 11%), non-Hodgkin's lymphoma (n = 4, 14%), Hodgkin's disease (n = 4, 14%) and acute nonlymphoblastic leukemia (n = 10, 38%). The length of stay for each readmission was 25 +/- 21 days. The median day of readmission was +62.5 (range = +19 to +987); however, 75% occurred between days +30 and +70. The causes of hospitalization were: infections (n = 24, 54%), due to the graft (n = 14, 31%), graft failure (n = 4, 9%), coagulation disorders (n = 2, 4%), and second neoplasm (n = 1, 2%). Mortality due to the transplant was 10 patients (14%) including: graft-versus-host disease (n = 3), sepsis (n = 3), thrombotic thrombocytopenic purpura (n = 1), and relapse (n = 3). CONCLUSIONS: Although there was a frequent use of hospital resources (20%) after HSCT with patients hospitalized for a median of 25 days, it was beneficial since there were 86% survivors at 36 months follow-up.

[Effectiveness of typical and atypical neuroleptics in the control of behavioral and psychopathological symptoms of dementia. Results of a retrospective study]. / Effectividad de los neurolépticos típicos y atípicos en el control de los síntomas conductuales y psicopatológicos de la demencia. Resultados de un estudio retrospectivo.

INTRODUCTION: Presence of disruptive behavioural and psychological symptoms in dementia (BPSD) is highly prevalent and, as a consequence, neuroleptics are frequently used in these patients to control BPSD. Several reviews have shown the clinical equivalence of different classes of neuroleptics in BPSD control, although that equivalence has been only indirectly assessed by comparing the combined results of different types of active drugs versus placebo. Thus, little is known on the comparative effectiveness, head to head, of different neuroleptics on BPSD. The aim of this study was to gather preliminary information on the effectiveness of typical (haloperidol, thioridazine) and atypical (olanzapine, risperidone) neuroleptics on BPSD. METHODS: Multicenter, observational and retrospective study using chart reviews of patients with dementia to assess neuroleptic prescriptions and clinical outcomes at 12 weeks on treatment. RESULTS: No significant differences on BPSD improvement were found by type of neuroleptic (n=78; Kruskal- Wallis exact test; p=0.47). There also were no differences by neuroleptics when the analysis was stratified by levels of cognitive decline (Kruskal-Wallis exact test; p=0.86 and 0.87 for moderate and severe levels of deterioration, respectively). Recorded side effects were worse in the haloperidol group (n=19) regarding rigidity (Fisher's exact; p=0.01), tremor (Fisher's exact p=0.03) and akathisia (Fisher's exact; p=0.03). CONCLUSIONS: Our findings support the equivalence in effectiveness of several classes of neuroleptics commonly used to treat BPSD. Nevertheless these results need to be confirmed by adequately powered randomized trials and further pharmacoepidemiological studies to assess their safety.

Effect of type and level of fish oil supplementation on yolk fat composition and n-3 fatty acids retention efficiency in laying hens.

1. Laying hen performance and yolk fat fatty acid (FA) concentrations were evaluated with respect to the inclusion in the diet of different sources and levels of marine fish oil (MFO). 2. Twelve diets were arranged factorially, with three sources (MFO1, MFO2_EPA, MFO3_DHA) and four levels of inclusion (15, 30, 45 and 60 g/kg) of MFO. 3. Type of diet had little effect on egg production traits, although laying rate and shell thickness slightly decreased at the highest level of MFO supplementation. 4. An increase in level of inclusion of MFO from 15 to 60 g/kg linearly increased concentrations of C20:5 n-3, C22:5 n-3, C22:6 n-3 and total n-3 FA in yolk fat, but greatly impaired their efficiencies of deposition (g retained/g ingested). 5. An interaction between type and dietary concentration of MFO was found, as the reduction in efficiency of retention of n-3 FA in egg fat with level of MFO was less when the proportion of n-3 in total FA decreased or when that of DHA in total n-3 FA increased. 6. MFO3_ DHA was more efficiently used for total n-3 FA yolk deposition than MFO2_EPA at a similar total n-3 FA intake. 7. Dietary inclusion of MFO reduced LC n-6 FA yolk fat content, which additionally decreased the ratio between total n-6 and total n-3 FA in egg fat. 8. Regression equations were calculated in order to predict efficiency of retention and n-3 FA concentration of yolk fat in the range of diets studied.

Effects of dietary conjugated linoleic acid and high-oleic sunflower oil on performance and egg quality in laying hens.

(1) Laying hen performance, yolk fatty acid (FA) concentrations, sensory quality and firmness of eggs were evaluated with respect to the inclusion in the diet of conjugated linoleic acid (CLA) and high-oleic acid sunflower oil (HOSO). (2) Nine diets were arranged factorially, with three concentrations of CIA (0, 1 and 2 g/kg) and HOSO (10, 20 and 30 g/kg). (3) Type of diet did not affect egg production traits. (4) Dietary addition of CLA decreased yolk lipid content and yolk lipid concentrations of monounsaturated FA, C(20:4 n-6) and C(22:6 n-3), but increased those of CLA and saturated FA. (5) Dietary addition of HOSO increased monounsaturated FA concentrations in the yolk lipid but decreased those of CLA and saturated FA. (6) CLA supplementation increased yolk moisture and firmness and impaired the sensory quality of eggs. (7) An interaction between CLA and HOSO addition was found as effects of CLA addition on yolk lipid CLA concentrations and egg quality traits were smaller when the amount of HOSO in the diet increased. (8) Regression equations have been calculated in order to predict yolk CLA and C(18:1), concentration from dietary composition, and yolk firmness from yolk FA composition.

Effects of dietary conjugated linoleic acid and fish oil supplementation on performance and egg quality in laying hens.

1. Laying hen performance, yolk fat fatty acid concentrations and firmness of eggs were evaluated with respect to the inclusion in the diet of conjugated linoleic acid (CLA) and fish oil. 2. Nine diets were arranged factorially, with three levels of supplementation of CLA (1, 3 and 5 g/kg) and fish oil (0, 14 and 20 g/kg). 3. Type of diet did not affect egg production traits. 4. CLA addition increased yolk weight and yolk fat concentrations of CLA, saturated and total long-chain n-3 fatty acids, but decreased those of monounsaturated and total long-chain n-6 fatty acids. 5. Fish oil addition increased long-chain n-3 fatty acids yolk fat concentrations but decreased those of CLA, saturated and long-chain n-6 fatty acids. 6. Effects of CLA addition on yolk fat concentrations of C22:4 n-6 and C20:5 n-3 were greater when no fish oil was added to the diet. 7. CLA supplementation increased linearly yolk moisture and firmness and altered albumen and yolk pH.

Effect of levels of starch, fiber, and lactose on digestion and growth performance of early-weaned rabbits.

The effect of source of carbohydrate on gut histology, digestion efficiency, and growth performance in early-weaned (25 d) rabbits at the starter period (25 to 39 d) was investigated. Six diets were factorially arranged to study the effect of partial substitution of starch (0, 25, or 50%) by lactose at two levels of fiber (30 or 36% NDF). Diets were formulated to meet or exceed essential nutrient requirements of growing rabbits. A feeding trial was conducted to measure the effect of treatments on growth performance in 252 rabbits that were fed the experimental diets in the starter period and thereafter received a common feed until 60 d of age. Fecal apparent digestibility was determined at 35 d of age in nine animals per diet. The four diets with extreme lactose content were used to determine ileal apparent digestibility of starch and lactose (nine replicates per diet), weights of stomach and cecum, stomach pH, cecal fermentation traits, amylase and disaccharidase activities (10 animals per diet), and jejunal morphology (six animals per diet). Weaning increased (P < 0.001) amylase activity by 59% but decreased (P < 0.001) maltase, sucrase, and lactase activities by 30, 48, and 72%, in parallel with a reduction of villus height by 19%. Dietary NDF level did not affect either jejunal morphology or sucrase and lactase activities but increased amylase (P = 0.05) and maltase (P < 0.001) activities by 22 and 92%, respectively. Substitution of starch by lactose had no effect on jejunal morphology or enzymatic activity. Ileal lactose and starch digestibility were not affected by dietary NDF or lactose level and averaged 73.8 and 90.8%, respectively. Substitution of starch by fiber and lactose affected ileal flux of starch plus lactose (by -0.5 and +1.7 g/d) and cecal pH (by +2.1 and -2.8%, respectively). Fecal NDF digestibility was relatively low (23.1% on average) and was not affected by treatments, whereas that of lactose and starch was almost complete. An increase of dietary NDF level led to an impairment of ADG and feed efficiency in the starter (P < 0.002) and in the overall (P < 0.03) fattening period. Substitution of starch by lactose linearly decreased (P < 0.001) feed efficiency in the starter period and linearly increased (P < 0.001) diarrhea incidence in the fattening period. The results indicate that digestive capability of early-weaned rabbits is limited and should be taken into account to establish optimal levels and sources of carbohydrates in the starter diet.

Variability in the levels of PML-RAR alpha fusion transcripts detected by the laboratories participating in an external quality control program using several reverse transcription polymerase chain reaction protocols.

BACKGROUND AND OBJECTIVES: The detection of PML-RAR by reverse transcription (RT) polymerase chain reaction (PCR) in acute promyelocytic leukemia (APL) patients who are in hematologic remission influences therapeutic decision making in several trials. In the light of this, the Spanish group has recently designed an external quality assessment program (EQAP) of RT-PCR detection of PML-RAR, which includes a study of sensitivity of the participating laboratories. DESIGN AND METHODS: Eighteen laboratories were involved in the program. Ten laboratories followed the method of Biondi et al., 5 employed that of Borrow et al. and the 3 remaining used other protocols. The sensitivity was studied in five rounds of quality control. The first two shipments consisted of dilutions of NB4 RNA into non-APL RNA. The third round consisted of serial dilutions of the NB4 cell line into HL60 cells. The fourth and five rounds consisted of plasmid dilutions containing the bcr1 and bcr3 PML-RAR isoforms. RESULTS: The results showed that the distinct methods allow detection of the PML-RAR hybrid up to a dilution of 10(-4), and exceptionally, up to 10(-5). The laboratories following the method of Biondi et al. usually detected the 10(-3) dilution and less frequently the 10(-4) one, whereas those using other methods usually detected PML-RAR transcript in the 10(-4) dilution, and less commonly in the 10(-5) dilution. However, each of the PCR methods used by EQAP participating laboratories successfully detected at least 50 copies of PML-RAR alpha fusion transcript in plasmid dilution controls. INTERPRETATION AND CONCLUSIONS: The results point to heterogeneous sensitivity amongst participating laboratories. This may reflect differences in methodology, although variations in sample quality may also account for discrepant findings.

Effect of fiber source on cecal fermentation and nitrogen recycled through cecotrophy in rabbits.

The influence of fiber source on fiber digestion in rabbits was investigated. Six fibrous feedstuffs with wide differences in chemical composition and particle size were selected: paprika meal, olive leaves, alfalfa hay, soybean hulls, sodium hydroxide-treated barley straw, and sunflower hulls. Six diets were formulated to contain one of these ingredients as the sole source of fiber. To avoid nutrient imbalances, fiber sources were supplemented with different proportions of a fiber-free concentrate, based on soy protein isolate, wheat flour, lard, and a vitamin and mineral mix, to obtain diets containing at least 3% nitrogen and 5% starch. Daily soft feces excretion, and its NDF, and total and microbial nitrogen content were determined in 60 fattening rabbits (10 per diet). Seven days after the last cecotrophy control, the same animals were used to determine weight of stomach, cecum and their contents, and cecal fermentation traits (pH, VFA and ammonia concentrations, and buffer properties of cecal contents). Stepwise regression analysis showed a positive effect (P < .001) on soft feces excretion, total and microbial nitrogen concentrations in soft feces, cecal acidity, and total VFA in the cecum of dietary pectic constituents (2.9, 3.5, 2.5, .9, and 6.6%) and proportion of fine particles (< .315 mm) (1.8, .9, 1.3, .15, and .9%) per each increment of one percentage unit of the independent variables. Proportion of fine particles also increased weight of cecal contents (P < .001). Soft feces excretion and weight of stomach and of its contents increased (P < .001) by 5.2, 2.8, and 10.2% per each percentage unit increment of proportion of large particles (> 1.25 mm). Degree of lignification of NDF decreased total nitrogen concentration in soft feces and cecal VFA concentration (P < .001). Source of fiber affected cecal pH not only by its influence on the cecal concentrations of the final products of fermentation, but also through its effect on the pH of dry cecal contents (P < .001). The latter was negatively correlated with dietary proportion of fine particles, degree of lignification of NDF, and base-buffering capacity of dry cecal contents (r = -.52, -.37, and -.49, respectively). From these results, we conclude that pectic constituent concentration, degree of lignification of NDF, and particle size are the variables that best characterize the influence of the source of fiber on soft feces excretion and cecal fermentation traits in rabbits.

Effect of fiber source on cell wall digestibility and rate of passage in rabbits.

The influence of fiber source on fiber digestion and mean retention time was investigated. Six fibrous feedstuffs with wide differences in chemical composition and particle size were selected: paprika meal, olive leaves, alfalfa hay, soybean hulls, sodium hydroxide-treated barley straw, and sunflower hulls. Six diets were formulated to contain one of these ingredients as the sole source of fiber. To avoid nutrient imbalances, fiber sources were supplemented with different proportions of a concentrate free of fiber based on soy protein isolate, wheat flour, lard, and a vitamin and mineral mix to obtain diets containing at least 18.5% CP and 5% starch. Fecal apparent digestibility of nonstarch polysaccharides (NSPd) and its monomers, NDF, NDF-ADL, and ADF-ADL, were determined using four New Zealand White x California growing rabbits per diet. Total, ileorectal, and cecal mean retention times (tMRT, i-rMRT, and cMRT, respectively) were determined for diets based on paprika meal, olive leaves, soybean hulls, and sunflower hulls in 16 does (four per diet) fitted with T-cannulas at the terminal ileum. In both trials, DMI was negatively correlated with the proportion of fine particles (FP: < .315 mm) and positively correlated with the proportion of large particles (LP: > 1.25 mm) (P < .01). Stepwise regression analysis showed that FP was the dietary characteristic best related to digestibilities of NSP, uronic acids, glucose and NDF, tMRT, and cMRT (P < .001), showing a positive correlation with these variables. In all these cases, this procedure selected the proportion of large particles as a second variable in the model. Degree of lignification of NDF, considering lignin as the difference between ADL and acid detergent cutin, was only included as the third variable for the model of NDF digestibility. Digestibility of NSP was positively correlated with those of NDF, NDF-ADL, and ADF-ADL (r = .82, .87 and .85, respectively, P < .001); the latter was also highly correlated with the digestibility of the glucose included in the NSP fraction (r = .86; P < .001). Cecal mean retention time accounted for 63% of average tMRT, for most of the variability in tMRT (r = .99; P < .001), and was positively related to NSPd (r = .89; P < .001). From these results, we conclude that particle size is a major factor affecting fiber digestion efficiency, rate of passage, and feed intake in rabbits.

2-Amino-3-substituted-6-[(E)-1-phenyl-2-(N-methylcarbamoyl)vinyl]imid azo[1,2-a]pyridines as a novel class of inhibitors of human rhinovirus: stereospecific synthesis and antiviral activity.

A series of 2-amino-3-substituted-6-[(E)-1-phenyl-2-(N-methylcarbamoyl)vinyl]+ ++imid azo[1,2-a]pyridines 1a-i, structurally related to Enviroxime and its analogous benzimidazoles, was designed and prepared for testing as antirhinovirus agents. The imidazo ring in this class of compounds was constructed starting from the aminopyridine after tosylation and subsequent treatment with the appropriate acetamides. The key steps in the synthesis include the development and use of a new Horner-Emmons reagent for the direct incorporation of methyl vinylcarboxamide. The reaction was stereospecific in the substrates 5a-f leading exclusively to the desired E-isomer and avoiding the use of reverse-phase preparative HPLC for the separation of both possible isomers before antiviral activity evaluation. The isopropylsulfonyl group, known as the best substituent at the 1-position in the benzimidazole SAR in terms of activity, was introduced in this new series of imidazo[1,2-a]pyridines via halogen-metal exchange and subsequent treatment with isopropyl isopropanethiolsulfonate. Compounds 1a-i were evaluated in plaque reduction assay and in a cytopathic effect assay. Compounds 1b-d,h exhibited a strong antirhinovirus activity, and no apparent cellular toxicity was visible. The substitution at the 3-position was required for activity. Surprisingly the isopropylsulfonyl in this family of compounds did not enhance the activity as in the case of benzimidazoles. Instead, compound 1i was 4 times less active than its phenyl and sulfide partners. The chemistry as well as the biological evaluation are discussed.

High incidence of the CD8/9 (+G) beta 0-thalassemia mutation in Spain.

BACKGROUND AND OBJECTIVE: In Spain, as in other Mediterranean regions the most common beta-thalassemia mutations are due to point mutations in gene regions that are critical for production of mRNA, such as [IVS-I-nt1 (G-->A), IVS-I-nt6 (T-->C), IVS-I-nt110 (G-->A)] which interrupt normal RNA processing or nonsense mutations [CD39 (C-->T)] which interrupt the translation of mRNA. The frameshift mutation CD8/9 (+G) is a very common allele in Asian Indians but is rare in the Mediterranean regions in which isolated alleles with this mutation have been found in Israel, Greece, Portugal and Turkey. DESIGN AND METHODS: We performed a molecular analysis of 175 chromosomes corresponding to 233 beta-thalassemia patients (221 heterozygous, 10 homozygous and 2 compound heterozygous) who belong to 169 Spanish families. The study of beta-thalassemia was made by PCR-ARMS, the alpha genes by Southern blot, the phenotype of Hb Lepore by enzymatic amplification and the presence of -158 gamma G C-->T mutation by PCR and digestion with the restriction enzyme XmnL. RESULTS: Twenty of these 233 patients showed the beta-thalassemia mutation CD8/9 (+G) (17 were heterozygous, 2 homozygous and in one patient the mutation was associated with a structural variant Hb Lepore Boston). INTERPRETATION AND CONCLUSIONS: These data reveal the heterogeneity of beta-thalassemia in Spain and the relatively high frequency (8.6%) of the frameshift mutation CD8/9 (+G). It is surprising that homozygotes for beta zero-thalassemia due to this mutation with very high Hb F values (around 90%) present a phenotype of intermediate thalassemia.

Leukaemia of natural killer cell large granular lymphocyte type with HLA-DR-CD16-CD56bright+ phenotype.

The case is reported of a 45 year old woman with the rare leukaemia of natural killer cell large granular lymphocyte (NK/ LGL) type. Cytometric analysis of leukaemic blasts showed that they were positive for CD2, CD38, and CD56 antigens but negative for a series of antigens including CD3, CD7, CD16, and HLA-DR. Rearrangements of the beta T cell receptor, and heavy and kappa immunoglobulin genes were not detected and neither were chromosomal abnormalities. Leukaemic blasts developed NK cytotoxicity. The patient failed to respond to aggressive chemotherapy and died three months after diagnosis. The lack of expression of HLA-DR is an extraordinary characteristic of this case, as all cases of acute NK cell leukaemias described to date expressed HLA-DR. The immunophenotype observed in the NK cell leukaemic blasts may represent the counterpart of a hypothetical normal cell precursor in an early stage of ontogenic NK cell development.

The response of highly productive rabbits to dietary sulphur amino acid content for reproduction and growth.

This study investigated the sulphur amino acid (SAA) requirements of rabbits. Five diets, containing 0.48-0.72% crude SAA, were formulated by supplementing a basal diet with DL-methionine. The apparent methionine digestibility (%) was 71.4 +/- 1.1 in the basal diet and 102.9 +/- 0.9 for DL-methionine, as estimated by the difference method. Feeding trials were carried out using 370 rabbit does and 1 195 weanling rabbits slaughtered at 2-2.1 kg body weight. Milk production was measured in 80 lactations. Carcass traits were determined in 125 rabbits. The dietary SAA content affected several productive traits, such as milk production, parturition interval, growth rate, carcass quality and feed efficiency. When the diets were compared using orthogonal contrasts, a minimum requirement of 0.54% crude or 0.40% digestible SAA was determined. Further responses in performance were observed, however, when the data were analysed by regression methods. The values of crude and digestible SAA for optimal production were, respectively, 0.63 and 0.49% (rabbit does) and, at least, 0.72 and 0.58% (growing rabbits).

Effect of substitution of starch for fiber and fat in isoenergetic diets on nutrient digestibility and reproductive performance of rabbits.

The optimal level of starch in diets for rabbit does was investigated. Five isoenergetic and isoproteic diets containing 26.6, 24.6, 19.0, 16.8, or 13.0% starch and 31.2, 33.4, 36.0, or 41.2% NDF, respectively (DM basis), were made by substitution of starch for NDF and fat. The effect of diet on nutrient digestibility was determined in fattening and nonlactating and lactating adult does using a total of 105 rabbits. Increasing dietary starch content linearly increased (P < .001) DM, GE, CP (P = .07), and starch digestibilities but decreased (P < .001) NDF digestibility. Nutrient digestibility was higher (P < .05), except for CP, in adult does than in fattening rabbits. Dry matter and GE digestibilities were higher (P = .08) for nonlactating than for lactating does. A lactation trial using 440 rabbit does was conducted over a 6-mo experimental period. Milk production and milk composition were measured in 70 lactations. A decrease in dietary starch content did not improve pup mortality before weaning but impaired (linear, P < .001) dry feed intake and pup growth from 21 d until weaning. Diet did not influence does' feed intake, milk DM, ether extract, and CP contents or prolificacy. However, diet had quadratic effects on milk production (P = .15), milk lactose content (P = .07), parturition interval (P = .02), and feed conversion efficiency (P = .02), expressed both per weight or number of pups weaned. Optimal values were reached for dietary starch and NDF contents at approximately 20 and 35.5% (DM basis), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)