Egg quality, fatty-acid composition and gastrointestinal morphology of layer hens fed whole flaxseed with enzyme supplementation.

1. Flaxseed is a rich source of α-linolenic acid (ALA, 18:3 n-3). Feeding flaxseed to hens can increase n-3 fatty acids (FA) in eggs. However, non-starch polysaccharides (NSP) in flaxseed decrease nutrient digestibility and can have a negative impact on egg n-3 FA incorporation. Addition of carbohydrase enzymes to flaxseed-based diets can decrease the anti-nutritive effects of NSP. 2. An experiment was conducted to investigate the effect of enzyme supplementation on FA composition and gastrointestinal morphology in hens fed flaxseed. A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial. 3. Egg weight was highest in hens fed Flax+E1 (P < 0.05). Yolk weight was higher in Flax+E1 compared with the control and Flax+E2 and was not different from Flax treatment. ALA and total n-3 FA was highest in eggs from Flax+E2 hens (P < 0.05). Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05). Over nine-fold increase in hepatic ALA was observed in the liver of hens fed flaxseed-based diets when compared with the control diet (P < 0.0001). No effect of enzyme supplementation was observed on liver ALA, DHA or long chain n-3 FA (P > 0.05). Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05). 4. Villi height and width was higher in the duodenum and jejunum of hens fed flax-based diets compared to the control (P < 0.05). Enzyme supplementation led to an increase in villi width in jejunum (P < 0.05) in hens fed Flax+E2 (P < 0.05). No effect of diet was observed in the crypt depth and villi height:crypt depth ratio in the jejunum (P > 0.05). 5. It was concluded that enzyme supplementation enhanced total n-3 FA deposition in eggs and liver and influence gastrointestinal morphology in layer hens fed flaxseed.

Expression of the SNT-1/FRS2 phosphotyrosine binding domain inhibits activation of MAP kinase and PI3-kinase pathways and antiestrogen resistant growth induced by FGF-1 in human breast carcinoma cells.

Fibroblast growth factor (FGF) signaling can bypass the requirement for estrogen receptor (ER) activation in the growth of ER-positive (ER+) breast cancer cells. Fibroblast growth factor-1 stimulation leads to phosphorylation of the adaptor protein Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target (SNT-1) on C-terminal tyrosine residues, whereas it is constitutively bound through its N-terminal phosphotyrosine-binding domain (PTB) to FGF receptors (FGFRs). By expressing the PTB domain of SNT-1 (SNT-1 PTB) in an inducible manner in an ER+ breast carcinoma line, ML20, we asked whether we could uncouple FGFR activation from its downstream signaling components and abrogate FGF-1-induced antiestrogen-resistant growth. Induction of SNT-1 PTB resulted in a significant decrease of FGF-1-dependent tyrosine phosphorylation of endogenous SNT-1, strong inhibition of complex formation between SNT-1, Gab-1 and Sos-1, and reduced activation of Ras, mitogen-activated protein kinase (MAP kinase), and Akt. SNT-1 PTB also inhibited the phosphorylation of p70S6K on Thr421/Ser424 and Ser411, which may result from the abrogation of MAP kinase activity. Moreover, we also observed a decreased phosphorylation of the MAP kinase-independent site Thr389. This may reflect both inhibition of PI-3 kinase pathways and mammalian target of rapamycin (mTOR)-dependent signaling, as the phosphorylation of Thr389 site was sensitive to treatment with the PI3-K and mTOR inhibitors, LY294002 and rapamycin, respectively. Collectively these results suggest that SNT-1 plays a pivotal role in FGF-dependent activation of the Ras-MAP kinase, PI-3 kinase, and mTOR pathways in these cells. Fibroblast growth factor-1 dependent colony formation of ML20 cells in media containing the pure antiestrogen ICI 182,780 was also markedly inhibited upon induction of SNT-1 PTB, suggesting that blockade of FGFR-SNT-1 interactions might abrogate FGF-mediated antiestrogen resistance in breast cancers.

Emotional outbursts and post-traumatic stress disorder during intracarotid amobarbital procedure.

Severe emotional outbursts (SEOs) during intracarotid amobarbital procedures (IAP) rarely jeopardize preoperative language and memory testing. Four of four patients (100%) with outbursts had experienced significant emotional trauma (three were raped and one witnessed a decapitation), compared with 26 of 546 patients (4.8%) without outbursts (chi2 = 69.8, p < 0. 0001). Evocative injections were ipsilateral to seizure focus. IAP may disrupt emotional balance in some traumatized patients. Counseling may prevent SEOs.

An estimate of the prevalence of asthma and wheezing among inner-city children.

OBJECTIVE: To estimate the prevalence of asthma and wheezing unassociated with a diagnosis of asthma among inner-city children. DESIGN: Cross-sectional survey of a sample of Bronx households. METHODS: Random digit dialing telephone survey using parental report. SETTING: Bronx County, NY. PARTICIPANTS: 662 self-designated heads-of-household who reported for all children 0 through 17 years of age living in their households. MEASUREMENTS: Questions from the Child Health Supplement to the 1988 National Health Interview Survey and the International Union Against Tuberculosis and Lung Disease Bronchial Symptoms Questionnaire were used to estimate the prevalence of asthma and wheezing-related illness. RESULTS: Information was gathered on 1285 children. Of this sample, 184 (14.3%) were reported to have ever had asthma (cumulative prevalence) and 111 (8.6%) were reported to have asthma in the last 12 months (period prevalence). The asthma period prevalence rate among Bronx children was twice the United States rate (4.3%). Among children 0 through 11 years of age, the prevalence rate was similar for boys and girls, although among children 12 through 17 years of age, asthma was significantly more prevalent among boys. Fifty-four children (4.2%) were reported to have had wheezing in the past 12 months unassociated with a diagnosis of asthma (wheeze only). The cumulative, but not the period, prevalence rate of asthma differed significantly by income and race/ethnicity. The cumulative prevalence was significantly higher among Hispanics and children from the lowest income families. The prevalence of wheeze only (no reported history of asthma) was higher among whites (6.4%) and blacks (5.8%) than Hispanics (2.9%) (P < .1). The reported number of wheezing attacks and the average number of nights per week that sleep was disturbed by wheezing during the past year were similar for those with asthma and those with wheeze only, although severe attacks (wheezing severe enough to limit speech) were significantly more likely among those reported to have asthma (P < .001). The total asthma prevalence (period prevalence of asthma plus wheeze only) was 12.8% and was quite consistent across subgroups. CONCLUSIONS: These data suggest that the prevalence of asthma among inner-city children may be substantially higher than the rates for this group estimated from national survey data. Some proportion of the wheeze only group may represent undiagnosed, and thereby undertreated, asthma. Public health efforts directed at reducing asthma morbidity and mortality need to address the possibility that asthma prevalence is higher within inner cities and that a large number of children with asthma may be inadequately diagnosed and treated.

Activity of triciribine and triciribine-5'-monophosphate against human immunodeficiency virus types 1 and 2.

Triciribine (TCN) and its 5'-monophosphate (TCN-P) are novel tricyclic compounds with known antitumor activity; TCN-P is currently in phase II human clinical trials. We now report that these compounds have potent and selective activity against HIV-1 and HIV-2. Using a syncytial plaque assay, TCN and TCN-P were active against HIV-1 at 0.01-0.02 microM and had differential selectivities of 2250 and 1900, respectively, compared to 1850 for AZT. In contrast, TCN and TCN-P had minimal selectivity against human cytomegalovirus (50 and 27, respectively). TCN and TCN-P markedly inhibited HIV-1-induced p24 core antigen production, reverse transcriptase, and infectious virus production in a dose-dependent manner using HIV-1 acutely infected CEM-SS, H9, and persistently infected H9IIIB and U1 cells. In acutely infected PBL cells, TCN and TCN-P inhibited reverse transcriptase and infectious virus production but not p24 core antigen production. Using a microtiter XTT assay, TCN and TCN-P were active against a panel of HIV-1 and HIV-2 strains at IC50 values ranging from 0.02 to 0.46 microM. Evaluation of matched pairs of predrug and postdrug therapy HIV-1 isolates established that AZT-resistant and TIBO-resistant variants of HIV-1 were sensitive to TCN or TCN-P. Furthermore, unlike AZT and other fraudulent nucleosides, neither TCN, TCN-P, nor TCN-TP inhibited the viral reverse transcriptase. Thus, even though triciribine is a nucleoside chemically, it does not act biologically by classic nucleoside modalities but rather by a unique mechanism yet to be elucidated.

An ELISA system for evaluating antiretroviral activity against Rauscher murine leukemia virus.

A system for evaluating the activity of antiviral agents against Rauscher murine leukemia virus (R-MuLV) has been developed using an enzyme linked immunosorbent assay technique. The activity of various antiviral compounds demonstrated in this assay system has been compared to their activity in the UV-XC plaque reduction assay, which has been used historically for evaluating anti-R-MuLV compounds. The assay is based upon detection of R-MuLV encoded p30 protein production in virus infected murine cells. The assay reagents are readily available and the assay system is amenable to automated data collection systems. Cytotoxicity evaluations are conducted in parallel to the Rauscher MuLV ELISA assay in order to assess drug-induced reductions in cell viability. Cytotoxicity evaluations are important to interpretation of the ELISA results since reductions in cell viability reduce viral protein production which would indicate an antiviral drug effect. This system is less sensitive than the classical UV-XC plaque reduction assay; however, it does offer an alternative to the time-consuming and labor-intensive plaque assay.

In vitro and in vivo enhancement of ddI activity against Rauscher murine leukemia virus by ribavirin.

Ribavirin has been reported to enhance the activity of ddI against HIV. We explored this enhancement of antiviral activity in Rauscher murine leukemia virus (RMuLV) models in vitro and in vivo. The significant finding in these studies was that combinations of the drugs exhibited virus titer reductions that were greater than would be expected if the drug interactions were simply additive. These effects were designated synergistic by the method of Prichard and Shipman (Prichard, M.N. and Shipman, C., Jr. (1990). A three-dimensional model to analyze drug-drug interaction, Antiviral Res. 14, 181-206). In addition to the antiviral synergy, we also observed some synergistic toxicity in the animal model.

Thiazolobenzimidazole: biological and biochemical anti-retroviral activity of a new nonnucleoside reverse transcriptase inhibitor.

Thiazolobenzimidazole (NSC 625487) was a highly potent inhibitor of human immunodeficiency virus-induced cell killing and viral replication in a variety of human cell lines, as well as fresh human peripheral blood lymphocytes and macrophages. The compound was active against a panel of biologically diverse laboratory and clinical strains of HIV-1, including the AZT-resistant strain G910-6. However, the agent was inactive against HIV-2 and a pyridinone-resistant strain (A17) of HIV-1, a strain which is cross-resistant to several structurally diverse members of a common pharmacologic class of nonnucleoside reverse transcriptase inhibitors. The compound selectively inhibited HIV-1 reverse transcriptase but not HIV-2 reverse transcriptase. Combinations of thiazolobenzimidazole with either AZT or ddI synergistically inhibited HIV-1 induced cell killing in vitro. Thiazolobenzimidazole also inhibited the replication of the Rauscher murine leukemia retrovirus. Thus, thiazolobenzimidazole is a new active anti-HIV-1 chemotype and may represent a subclass of nonnucleoside reverse transcriptase inhibitors with an enhanced range of anti-retroviral activity.

Comparison of the use of reserpine versus alpha-methyldopa for second step treatment of hypertension in the elderly.

A retrospective chart analysis was conducted on all new elderly hypertensive patients referred to a community hypertension clinic who were being treated with either reserpine or alpha-methyldopa plus a diuretic. There were no significant differences between the two groups on entry in age, gender, co-morbid diagnoses, or systolic or diastolic blood pressure. There were no significant differences between the two groups in terms of side effects over three years, but the proportion of persons having compliance problems was significantly lower in the reserpine group. Mean diastolic pressures were significantly lower after one, two, and three years, and systolic pressures were lower after one and two years in the reserpine group. Reserpine is at least as effective as alpha-methyldopa in treating hypertension in the elderly and is associated with fewer problems in compliance.

Optimization of the reverse transcriptase assay for the detection of viral burden in mice infected with Rauscher murine leukemia virus.

Rauscher murine leukemia virus induces an erythroleukemia in susceptible strains of mice that is associated with splenomegaly and viremia. This animal model has been used for evaluating the in vivo efficacy of potential anti-HIV agents. The in vivo antiviral activity of therapeutic agents has usually been determined by measuring a reduction in the spleen weights of compound-treated mice or by quantitating viremia with the UV-XC plaque assay. The UV-XC assay, however, is time-consuming and labor-intensive. Virions of Rauscher murine leukemia virus, like other retroviruses, contain the enzyme reverse transcriptase. Quantitating the level of this enzyme in infected mouse sera provides a more rapid measure of viremia in the animal. We have examined the effects of several reagents, including detergent, KCl, EGTA, dGMP, spermine, as well as protease and RNase inhibitors, on the reverse transcriptase assay. The optimized assay method was effective in evaluating the antiviral activity of AZT in the Rauscher murine leukemia virus in vivo model. The assay is also amenable to automation if large numbers of assays are required.

Plant-derived and semi-synthetic calanolide compounds with in vitro activity against both human immunodeficiency virus type 1 and human cytomegalovirus.

Plant-derived and semi-synthetic calanolide compounds with anti-human immunodeficiency virus type 1 (HIV-1) activity were tested for anti-human cytomegalovirus (HCMV) activity in both cytopathic effect inhibition and plaque reduction assays. The results indicated that the anti-HCMV activity of calanolide compounds does not correlate with their activity against HIV-1. The semi-synthetic 12-keto derivatives tended to be more active against HCMV than the corresponding 12-OH congeners, which were more active against HIV-1. It appeared that the 7,8-unsaturated double bond in the chromene ring played a certain role in maintaining activities against both HCMV and HIV-1. Saturation of the double bond increased the EC50 values against both viruses, with concomitant increase in toxicity. The calanolide compounds reported here are the first non-nucleoside analogues capable of inhibiting both HIV-1 and HCMV and, therefore, may be useful chemoprophylactic agents for HCMV in HIV-infected people or vice versa.

Cross-cultural and multi-ethnic dementia evaluation by mental status and memory testing.

Two studies investigated aspects of cross-cultural dementia evaluation. The first explored consequences of using different mental status tests; the second compared mental status and memory assessments for normal individuals aged 70-79 and 80-89 in Japan and in America. In a dementia screening clinic, scores from the Hasegawa mental status test could be converted to the Blessed scale without influencing patient classification (impaired vs. unimpaired). Younger subjects were slightly superior to older subjects in mental status in both comparison groups. Both Japanese groups performed better on the memory test than even the younger American group.

Side effects and complications of cervical epidural steroid injections.

Two hundred and four cervical epidural injections of corticosteroids were performed on 142 patients for the treatment of cervical pain over a 1-yr period. Injections were performed at the C7-T1 interspace with 10-15 mL of 0.5% lidocaine containing 1 mg per kg of methylprednisone acetate. Four complications occurred: two dural punctures without sequelae; one episode of upper extremity weakness, which resolved in 24 hr; and one episode of nausea and vomiting lasting 12 hr. In addition, two side effects were frequently reported: stiff neck lasting 12-24 hr occurred in 13.2% of patients, and a mild facial flushing with subjective (but not objective) fever lasting about 12 hr occurred in 9.3% of patients. In this large series, the procedure appears safe to use in an outpatient setting.

Effectiveness of alprazolam in the treatment of chronic pain: results of a preliminary study.

One hundred chronic pain patients were begun on alprazolam, 1.5 mg/day. No other medication changes or therapeutic interventions were made. Sixteen patients were lost to follow-up and 1 oncology patient died. Of the 83 patients who were evaluated at 12 weeks, 61 (73.5%) showed improvement, and only 5 had discontinued the medication because of side effects. The average score of all patients had decreased from 3.6 to 2.2 on a verbal analog scale that rated pain severity from 0 to 5. There was no difference in response among the various diagnostic groups represented in the study population.

Influence of 1-dodecylazacycloheptan-2-one (Azone) on the topical therapy of cutaneous herpes simplex virus type 1 infection in hairless mice with 2',3'-di-O-acetyl-9-beta-D-arabinofuranosyladenine and 5'-O-valeryl-9-beta-D-arabinofuranosyladenine.

The predictive value of a recently developed physical model was tested in the topical treatment of cutaneous infections caused by herpes simplex virus type 1 in hairless mice with two ester prodrugs of 9-beta-D-arabinofuranosyladenine (ara-A) (1). The tests were conducted with 2',3'-di-O-acetyl-ara-A (4) and 5'-O-valeryl-ara-A (3) topically applied with and without 15% 1-dodecylazacycloheptan-2-one (2) (Azone), a percutaneous penetration enhancer. In addition to the in vivo studies, in vitro diffusion cell experiments with excised, full-thickness skin from hairless mice were conducted to determine the penetration enhancement effects of 2. As previously observed, 2 was able to induce remarkably large (100- to 1000-fold) flux enhancements in these in vitro experiments. Consistent with predictions based on the physical model studies, formulations of 3 and 4 without 2 had little or no influence on the pathogenesis of the herpes simplex virus type 1 infections; when 2 was present in the formulations, both 3 and 4 had dramatic therapeutic effects consistent with the predictions made with the physical model. Prodrug 4 with 2 was especially efficacious in the prevention of virus-induced lesions and in the survival of all animals. Similar results were obtained with acyclovir plus 2 in this model system.

Timing of coronary stent thrombosis in patients treated with prophylactic tirofiban.

BACKGROUND: Acute and subacute stent thromboses (ASST) are the major thrombotic complications of coronary stenting. The time course of ASST seems to be related to the type of antithrombotic therapy (four days in patients treated with aspirin and coumadin compared to 12 hours with the use of aspirin and ticlopidine). In this report, we compared the timing of ASST in patients treated with aspirin, ticlopidine/clopidogrel, heparin and tirofiban with that in patients treated with the same drugs but without tirofiban. METHODS: Retrospective analysis of the Hermann intervention database between January 1997 and October 1999 was performed. We identified 13 patients who required reintervention in the first week after a successful coronary stenting ( 1 stent). Four patients were treated with tirofiban (Group 1) and 9 were not (Group 2). RESULTS: The median time from stent deployment to ASST was 7 hours (interquartile range, 2.5Eth 33 hours) in group 2 compared to 84.5 hours (interquartile range, 56Eth 124.5 hours) in group 1. The mean time from stent deployment to ASST was 90.3 +/- 43.1 hours in group 1 versus 12.8 +/- 15.3 hours in group 2 (p = 0.0005). All episodes of ASST occurred 3 days in patients treated with tirofiban, whereas they occurred in the first 2 days in all patients not treated with tirofiban. CONCLUSION: Prophylactic tirofiban treatment delays the time to stent thrombosis after successful coronary artery stent implantation for more than two days. Patients at high risk for stent thrombosis treated with short-acting glycoprotein IIb/IIIa platelet receptor inhibitors may warrant close follow-up during the first week after stenting.

Comparison of adjustment of school-age children with and without chronic conditions: results from community-based samples.

We assessed whether children in the 1990s who were identified as having chronic conditions by using a new noncategorical technique (the Questionnaire for Identifying Children with Chronic Conditions) were as well adjusted as children without chronic conditions, and whether selection factors or sociodemographic variables accounted for any observed differences. Random-digit-dial telephone surveys were conducted using two separate samples: one consisting of 1275 children in 654 inner-city households and the other of 1388 children in a national sample of 712 households. Children with chronic conditions had poorer parent-reported functioning on the Personal Adjustment and Role Skills Scale total score and three of its six subscales (Hostility, Dependency, and Productivity). Differences in two other subscales (Withdrawal and Anxiety/Depression) were significant only for the inner-city sample. The results were consistent when controlling for other potentially confounding factors. These findings demonstrate that mental health risks continue to occur among contemporary community-based samples of children with chronic health conditions who are identified by using noncategorical techniques. These risks have implications for the care of those children.