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PubMed1981

Developing a model for health education interventions in the hospital setting.

Health education interventions in hospitals represent a factor of major influence with regard to the effectiveness of treatment and the prevention of relapse. A purposeful health education system aimed at patients, their families and friends has therefore been developed in the USSR after due experimentation. As regards patients, focus is placed on raising their level of knowledge about adequate health behaviour during hospitalization and after discharge, in order to prevent relapses, acute states and complications. Topics covered include regimen, diet, physical exercise, developing resistance to cold, giving up harmful habits (smoking, for example), etc. This includes individual, semi individual, semi group and group activities at all stages of the patient's stay in hospital. The mass media supplements this approach through hospital radio and TV programmes and popular scientific literature from the hospital library. For patients' relatives and friends, a programme of individual talks has been developed. Another facet of health education involves correspondence with patients and their relatives, to whom special leaflets are distributed. Preliminary evaluation carried out by public health administrators and health education workers indicates that the system yields satisfactory results.

Family↗
PubMed1992

Human monoclonal Fab fragments derived from a combinatorial library bind to respiratory syncytial virus F glycoprotein and neutralize infectivity.

Respiratory syncytial virus (RSV) is the most important cause, throughout the world, of severe viral lower respiratory tract illness in young children. Antibodies are known to mediate resistance to RSV infection and illness. We have isolated a number of human monoclonal Fab fragments to RSV F glycoprotein from a combinatorial antibody library expressed on the surface of phage. One of these neutralized a wide range of virus isolates, 10 subgroup A and 9 subgroup B isolates, with a titer (60% neutralization) of approximately 0.1-1.0 micrograms/ml. Another Fab neutralized diverse isolates at a concentration somewhat higher. These human Fab fragments show great promise for use in the prophylaxis or therapy of serious RSV lower respiratory tract disease. For intramuscular or intravenous administration, whole antibodies will be required, whereas for aerosol application, F(ab')2 or Fab fragments may suffice.

Amino Acid Sequence↗
PubMedDate not supplied

[Septic shock and selenium administration].

Selenium is an essential trace element. In the form of selenocysteine, an amino acid, selenium is necessary for the activity of important enzymes (i.e. glutathione peroxidases, thioredoxin reductase). In the periodic table of the elements, selenium belongs to the same column as oxygen. In fact, seleno-enzymes have an important role in the detoxification of reactive oxygen species, especially peroxides and hydroperoxides. In septic and septic-like shock patients, reactive oxygen species, particularly peroxides, play an important role through their destructive actions, which are favourable as critical components of microbial destruction and also deleterious in excessive generation. This excessive generation results in tissue damage. Moreover, reactive oxygen species modulate the activation of important intracellular mediators (NF kappa B activation, arachidonic acid cascade). Simultaneously in patients with severe infection, there is a marked and early plasma selenium decrease. Redistribution due to selective selenium uptake for metabolic use could be one of the main mechanisms for this decrease. This review was carried out by questioning on the one hand the Medline database, by consulting the reviews and works available in the services of biology, biochemistry and pharmacy, by a prospective follow-up on the subject in Current Contents, but also thanks to library searches carried out by Aguettant laboratories. Several supplementary studies at various doses (from 140 to 1000 micrograms/day sodium selenite) have been conducted, though only on small groups of patients and with a questionable design. Selenium treatment seem to be promising in severely septic patients. However, in the absence of pertinent clinical data, only the administration of doses below adverse effect levels, staying within physiological limits, can presently be recommended (i.e. 200 to 500 micrograms/day of sodium selenite).

Animals↗
PubMed1999

Powerful connections for public health: the National Library of Medicine and the National Network of Libraries of Medicine.

As incorporated in Healthy People 2010 objectives, data and information systems and a skilled workforce are 2 of the critical components of the public health infrastructure. The National Library of Medicine (NLM) and the National Network of Libraries of Medicine (NN/LM) are important resources for improving Internet access and providing related training to the public health workforce and to those in training for public health careers. The NLM and the NN/LM have joined forces with the Centers for Disease Control and Prevention, the Health Resources and Services Administration, the Association of State and Territorial Health Officials, the National Association of County and City Health Officials, and the Public Health Foundation. The goal of this collaboration is to improve electronic resources useful in public health practice and increase awareness of them, to train public health professionals to use electronic information services, and to help public health agencies obtain the equipment and Internet connections needed to use these services effectively. The databases, outreach programs, and connection grants available to public health professionals from the NLM, and the training and ongoing support available from the NN/LM for accessing these programs and services, are described.

Centers for Disease Control and Prevention, U.S.↗
PubMed2003

ArrayTrack--supporting toxicogenomic research at the U.S. Food and Drug Administration National Center for Toxicological Research.

The mapping of the human genome and the determination of corresponding gene functions, pathways, and biological mechanisms are driving the emergence of the new research fields of toxicogenomics and systems toxicology. Many technological advances such as microarrays are enabling this paradigm shift that indicates an unprecedented advancement in the methods of understanding the expression of toxicity at the molecular level. At the National Center for Toxicological Research (NCTR) of the U.S. Food and Drug Administration, core facilities for genomic, proteomic, and metabonomic technologies have been established that use standardized experimental procedures to support centerwide toxicogenomic research. Collectively, these facilities are continuously producing an unprecedented volume of data. NCTR plans to develop a toxicoinformatics integrated system (TIS) for the purpose of fully integrating genomic, proteomic, and metabonomic data with the data in public repositories as well as conventional (Italic)in vitro(/Italic) and (Italic)in vivo(/Italic) toxicology data. The TIS will enable data curation in accordance with standard ontology and provide or interface a rich collection of tools for data analysis and knowledge mining. In this article the design, practical issues, and functions of the TIS are discussed through presenting its prototype version, ArrayTrack, for the management and analysis of DNA microarray data. ArrayTrack is logically constructed of three linked components: a) a library (LIB) that mirrors critical data in public databases; b) a database (MicroarrayDB) that stores microarray experiment information that is Minimal Information About a Microarray Experiment (MIAME) compliant; and c) tools (TOOL) that operate on experimental and public data for knowledge discovery. Using ArrayTrack, we can select an analysis method from the TOOL and apply the method to selected microarray data stored in the MicroarrayDB; the analysis results can be linked directly to gene information in the LIB.

Databases, Factual↗
PubMed1992

Creating the future: IAIMS planning premises at the University of Washington.

In September 1990, the University of Washington (UW) received a Phase I IAIMS Planning Grant from the National Library of Medicine and embarked upon a planning process involving the entire health sciences center. As a result of our relatively late entry into IAIMS planning, we have been able to learn from the experiences of other health sciences centers and to leverage our existing institutional efforts. Consequently, our progress has been rapid, and in a little over a year, we drafted a long-range plan and embarked on several related research and development projects. The hallmarks of our planning process include careful study of both the UW institutional environment and the experiences of other IAIMS institutions throughout the United States; broad, interdisciplinary participation of faculty, librarians, and administrators; an intensive educational process; a focus on people rather than technology; and, above all, leveraging of existing institutional and research projects that support our vision for the future.

Computer Communication Networks↗
PubMed2005

The spectrum of informed consent in emergency psychiatric research.

STUDY OBJECTIVE: I evaluate the variation in requirements for informed consent in studies evaluating chemical tranquilization of agitated patients. METHODS: A computer-assisted literature search of the National Library of Medicine was performed. Additional use of the references listed in the articles identified with the search yielded 144 citations. Studies performed outside the United States were excluded, as were studies performed before the current US Food and Drug Administration regulations came into effect. Research not yet published but presented at national meetings was included, as was one study currently under way but otherwise meeting the inclusion criteria. Authors were contacted for further clarification in cases in which information was ambiguous or unavailable in print. RESULTS: Twelve studies were identified, and the approach to informed consent varied widely. The primary method of enrollment was informed consent in 7 studies. Three studies used a waiver of informed consent, but in these cases the federal regulations underlying these waivers varied. One study implied that neither consent nor a waiver of consent was needed. In one case, the primary method for consent was not specified. CONCLUSION: There is poor agreement about the application of current regulations about informed consent in emergency psychiatric research. Regulations are understood in such a variety of ways that they are effectively irrelevant. There needs to be much greater clarity about the use of waivers of informed consent in emergency research in general and emergency psychiatry in particular.

Drug Evaluation↗
PubMed1987

A novel progesterone-induced messenger RNA in rabbit and human endometria. Cloning and sequence analysis of the complementary DNA.

Complementary DNAs (cDNAs) prepared from messenger RNAs (mRNAs) isolated from endometria of 5 day pregnant rabbits were inserted into the plasmid pBR322. A library of 2400 recombinant plasmid clones was prepared and screened by differential in situ hybridization with cDNAs prepared from mRNAs of rabbits either injected with progesterone or untreated by the hormone. Clones encoding uteroglobin were identified and discarded. Several progesterone-induced and progesterone-repressed clones were identified. One of them corresponded to a relatively frequent mRNA (0.2% of clones in the library) of 2300 nucleotides. The induction of this messenger RNA by progesterone was totally suppressed by the antagonist RU486. This compound displayed a limited agonistic activity when administered alone. A very small increase in mRNA concentration was observed after estradiol administration. The messenger RNA was also found in the liver (where it was constitutively expressed), the ovaries, and the Fallopian tubes of rabbits. A cross-hybridizing messenger RNA was detected in human endometrium during the luteal phase. Sequence analysis showed that the messenger RNA encoded a protein of 370 amino acids with a calculated molecular weight of 40,800. A search in Genbank and National Biomedical Research Foundation data banks showed no identity or marked similarity with previously published DNA or protein sequences.

Animals↗
PubMed2005

Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis.

OBJECTIVES: Ageing in men is associated with a gradual decline in serum testosterone levels and a concomitant loss of muscle mass, accumulation of central adiposity, impaired mobility and increased risk of bone fractures. Whether androgen treatment might be beneficial in these subjects is still under debate. We have carried out a systematic review of randomized controlled trials (RCTs) evaluating the effects of testosterone (T) administration to middle-aged and ageing men on body composition, muscle strength, bone density, markers of bone metabolism and serum lipid profile. DATA SOURCE: A comprehensive search of all published randomized clinical trials was performed using the MEDLINE, Cochrane Library, EMBASE and Current Contents databases. REVIEW METHODS: Guided by prespecified criteria, software-assisted data abstraction and quality assessed by two independent reviewers, 29 RCTs were found to be eligible. For each investigated variable, we reported the results of pooled estimates of testosterone treatment using the random effect model of meta-analysis. Heterogeneity, reproducibility and consistency of the findings across studies were explored using sensitivity and meta-regression analysis. RESULTS: Overall, 1,083 subjects were evaluated, 625 randomized to T, 427 to placebo and 31 to observation (control group). Weighted mean age was 64.5 years (range 49.9--77.6) and mean serum testosterone was 10.9 nmol/l (range 7.8--19). Testosterone treatment produced: (i) a reduction of 1.6 kg (CI: 2.5--0.6) of total body fat, corresponding to -6.2% (CI: 9.2--3.3) variation of initial body fat, (ii) an increase in fat free mass of 1.6 kg (CI: 0.6--2.6), corresponding to +2.7% (CI: 1.1--4.4) increase over baseline and (iii) no change in body weight. The effects of T on muscle strength were heterogeneous, showing a tendency towards improvement only at the leg/knee extension and handgrip of the dominant arm (pooled effect size=0.3 standard mean difference (SMD), CI: -0.0 to 0.6). Testosterone improved bone mineral density (BMD) at the lumbar spine by +3.7% (CI: 1.0--6.4%) compared to placebo, but not at the femoral neck, and produced a consistent reduction in bone resorption markers (pooled effect size = -0.6 SMD, CI: -1.0 to -0.2). Testosterone also reduced total cholesterol by 0.23 mmol/l (CI: -0.37 to -0.10), especially in men with lower baseline T concentrations, with no change in low density lipoprotein (LDL)-cholesterol. A significant reduction of high density lipoprotein (HDL)-cholesterol was found only in studies with higher mean T-values at baseline (-0.085 mmol/l, CI: -0.017 to -0.003). Sensitivity and meta-regression analysis revealed that the dose/type of T used, in particular the possibility of aromatization, explained the heterogeneity in findings observed on bone density and HDL-cholesterol among studies. CONCLUSION: The present analysis provides an estimate of the average treatment effects of testosterone therapy in middle-aged men. Our findings are sufficiently strong to justify further interventional studies focused on alternative targets of androgenic treatment carrying more stringent clinical implications, in particular the cardiovascular, metabolic and neurological systems.

Adult↗
PubMed2000

Better access to information about clinical trials.

Access to information about clinical trials is important to researchers, health care professionals, and patients. Many have argued for the establishment of clinical trials registries, citing their substantial benefits. Although some registries do exist, it has been difficult to create comprehensive, easily accessible systems. This paper briefly reviews existing registries, discusses the challenges in building registries, and reviews some of their benefits. The paper concludes with a description of a new, extensive Web-based registry called ClinicalTrials.gov (http://clinicaltrials. gov/), which was developed at the National Institutes of Health (NIH) by the National Library of Medicine as a result of recent legislation calling for a comprehensive, publicly accessible registry of clinical trials. The first version of the system became available in late February 2000 and contains information about approximately 5000 trials. The first release contains primarily NIH-sponsored trials, and new trials are regularly added to the system. Subsequent versions will contain information about trials sponsored by other federal agencies and by the private sector. The system was developed in accordance with basic informatics principles, including adherence to standards, usability considerations, and iterative testing and evaluation.

Clinical Trials as Topic↗
PubMed1985

Characterization of recombinant monkey and human erythropoietin.

We have isolated the human EPO gene from a human genomic lambda library and a monkey EPO cDNA from an anemic monkey kidney cDNA library. These sequences have been expressed in both COS1 and Chinese hamster ovary cells. The expressed EPO has been shown to be fully biologically active both in vitro and in vivo and immunologically identical to the native hormone. In addition, administration of recombinant EPO to animals causes a dramatic increase in their hematocrit.

Anemia↗
PubMed2004

Office compared with ambulatory blood pressure in assessing response to antihypertensive treatment: a meta-analysis.

OBJECTIVE: To undertake a systematic review of the studies on the effect of antihypertensive treatment on ambulatory (ABP) and office blood pressure in order to obtain a differential assessment of the magnitude of the reduction in (1) office blood pressure compared with 24-h average ABP values, and (2) daytime compared with night-time average blood pressure values. DATA SOURCES: Medline search, Cochrane Library. REVIEW METHODS: This review is based on a meta-analysis (carried out according to the Quality of Reports of Meta-analyses of Randomized Controlled Trials Group statement, whenever applicable) of papers on the effect of antihypertensive drugs on blood pressure. Papers were selected if they provided information on drug-induced changes in one or both of: (1) both office blood pressure and 24-h ABP, and/or (2) both daytime and night-time average blood pressure. Additional inclusion criteria were administration of antihypertensive drugs for at least 1 week and good quality ABP, according to current guidelines. Comparison between the effect of treatment on blood pressure values was made by meta-regression of the data provided by the individual studies (weighted by their size) and by calculating differences between weighted average values obtained by pooling the results of individual papers. RESULTS: We identified 984 papers on this issue by Medline search, with no additional information from the Cochrane Library. The inclusion criteria were satisfied by only 44 papers, which were included in the final analysis. The results showed that treatment-induced reduction in blood pressure is both smaller for the 24-h average than for the office systolic and diastolic blood pressure and smaller for night-time than for daytime average diastolic blood pressure, the average ratio ranging from 0.67 to 0.75. A different ratio characterized the treatment-induced changes in office blood pressure and ABP in the Heart Outcomes Prevention Evaluation (HOPE) ABP substudy. CONCLUSIONS: The effect of antihypertensive treatment is greater on office blood pressure than on ABP, and is unevenly distributed between day and night. This suggests caution when interpreting trials on cardiovascular protection by antihypertensive treatment that are based only on office blood pressure readings, and advocates a more systematic adoption of ABP monitoring in these trials. The conflicting data provided by the main HOPE study and by the HOPE-ABP monitoring substudy on the role of blood pressure reduction in explaining the reduced event rates associated with treatment by angiotensin-converting enzyme inhibitors are a clear example of the importance of performing ABP monitoring in trials on cardiovascular protection.

Antihypertensive Agents↗
PubMed2000

Radiotherapy for the palliation of painful bone metastases.

BACKGROUND: Radiotherapy is used commonly to provide pain relief for painful bone metastases, and there is a perception that of the three-quarters of patients who achieve pain relief, half of these stay free from pain. However, the precise contribution from radiotherapy may be unclear because of difficulties in assessing the numbers of people achieving relief, the extent of relief and its duration, and the influence of other contemporaneous interventions, such as analgesics. OBJECTIVES: To assess pain relief from: 1. localised bone metastases achieved by radiotherapy, comparing the efficacy of different fractionation schedules 2. more generalised metastatic disease achieved by radiotherapy or radioisotopes. SEARCH STRATEGY: Studies were identified by searching Medline (1966 to August 1998), Embase (1980 to 1998), the Cochrane Library (1998 Issue 3) and the Oxford Pain Relief Database (1950 to 1994). SELECTION CRITERIA: The inclusion criteria used were: full journal publication, patients with pain due to bone metastases, and random allocation to a radiotherapeutic intervention (either external irradiation or administration of radioisotopes). DATA COLLECTION AND ANALYSIS: The number of patients achieving complete pain relief and at least 50% at one month were compared with an assumed natural history of 1 in 100 patients achieving pain relief without treatment to obtain the number-needed-to-treat (NNT). Summed pain relief or pain intensity difference over four to six hours was extracted, converted into dichotomous information yielding the number of patients with at least 50% pain relief, and used to calculate the relative benefit and the NNT for one patient to achieve at least 50% pain relief. MAIN RESULTS: Twenty trials reported on 43 different radiotherapy fractionation schedules and eight studies of radioisotopes. Radiotherapy produced complete pain relief at one month in 395/1580 (25%) patients, and at least 50% relief in 788/1933 (41%) patients at some time during the trials. There were no differences in the proportions of patients achieving these outcomes between single or multiple fraction schedules. The number-needed-to-treat (NNT) to achieve complete relief at one month (compared with an assumed natural history of 1 in 100 patients whose pain resolved without treatment) was 4.2 (95% CI 3.7-4.7). No pooled estimates of speed of onset of relief, or of its duration, could be obtained. In the largest trial (759 patients) 52% of those who had complete relief had achieved it within four weeks, and the median duration of complete relief was 12 weeks. For more generalised disease, radioisotopes produced similar analgesic results to external irradiation. Adverse effect reporting was poor. There were no obvious differences between the various fractionation schedules in the incidence of nausea and vomiting, diarrhoea or pathological fractures. REVIEWER'S CONCLUSIONS: Radiotherapy is clearly effective at reducing pain from painful bone metastases. There was no evidence of any difference in efficacy between different fractionation schedules, nor indeed of a dose-response with total dose of radiation. For treatment of generalised bone pain both hemibody irradiation and radioisotopes can reduce the number of painful new sites.

Bone Neoplasms↗
PubMed2006

S-adenosyl-L-methionine for alcoholic liver diseases.

BACKGROUND: Alcohol is a major cause of liver disease and disrupts methionine and oxidative balances. S-adenosyl-L-methionine (SAMe) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione, the main cellular antioxidant. Randomised clinical trials have addressed the question whether SAMe may benefit patients with alcoholic liver diseases. OBJECTIVES: To evaluate the beneficial and harmful effects of SAMe for patients with alcoholic liver diseases. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (May 2005), The Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 2, 2005), MEDLINE (1950 to May 2005), EMBASE (1980 to May 2005), and Science Citation Index Expanded (searched May 2005). SELECTION CRITERIA: We included randomised clinical trials studying patients with alcoholic liver diseases. Interventions encompassed per oral or parenteral administration of SAMe at any dose versus placebo or no intervention. DATA COLLECTION AND ANALYSIS: We performed all analyses according to the intention-to-treat method using RevMan Analyses provided by the Cochrane Collaboration. We evaluated the methodological quality of the randomised clinical trials by quality components. MAIN RESULTS: We identified nine randomised clinical trials including a heterogeneous sample of 434 patients with alcoholic liver diseases. The methodological quality regarding randomisation was generally low, but 8 out of 9 trials were placebo controlled. Only one trial including 123 patients with alcoholic cirrhosis used adequate methodology and reported clearly on all-cause mortality and liver transplantation. We found no significant effects of SAMe on all-cause mortality (relative risks (RR) 0.62, 95% confidence interval (CI) 0.30 to 1.26), liver-related mortality (RR 0.68, 95% CI 0.31 to 1.48), all-cause mortality or liver transplantation (RR 0.55; 95% CI 0.27 to 1.09), or complications (RR 1.35, 95% CI 0.84 to 2.16), but the analysis is based mostly on one trial only. SAMe was not significantly associated with non-serious adverse events (RR 4.92; 95% CI 0.59 to 40.89) and no serious adverse events were reported. AUTHORS' CONCLUSIONS: We could not find evidence supporting or refuting the use of SAMe for patients with alcoholic liver diseases. We need more long-term, high-quality randomised trials on SAMe for these patients before SAMe may be recommended for clinical practice.

Humans↗
PubMed2006

Gonadotrophins for idiopathic male factor subfertility.

BACKGROUND: Male factor infertility accounts for 50% of infertility. The treatment of idiopathic male infertility is empirical. Urinary, purified, and recombinant gonadotrophins have been used to improve sperm parameters in idiopathic male infertility with the goal of increasing pregnancy rates. Research addressing pregnancy rates in partners of men treated with gonadotrophins has had conflicting results and needs to be analysed. OBJECTIVES: To determine the effectiveness of gonadotrophin administration to men with idiopathic subfertility on spontaneous pregnancy rate and in assisted reproductive techniques (ARTs). SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (19 November 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, issue 4, 2004), MEDLINE (1966 to April 2005), EMBASE and Biological Abstracts (1980 to November 2004). Searches were not limited by language. The bibliographies of included, excluded trials and abstracts of major meetings were searched for additional trials. Authors and pharmaceutical companies were contacted for missing and unpublished data. SELECTION CRITERIA: Truly randomised controlled trials where gonadotrophins were administered for the treatment of idiopathic male subfertility with reporting of pregnancy rates were included in the review. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. We analysed data regarding pregnancy occurring within 3 months after gonadotrophin therapy. MAIN RESULTS: Four RCTs with 278 participant were included in the analysis. None of the studies had an adequate sample size and they had variable follow-up periods. None of the studies reported live birth or miscarriage rates. Compared to placebo or no treatment, gonadotrophins showed a significantly higher pregnancy rate per couple randomized within 3 months of completing therapy (OR 3.03, 95% CI 1.30 to 7.09). Pregnancy rate was 13.4% (19/142) in the gonadotrophin group and 4.4% (6/136) in the control group. AUTHORS' CONCLUSIONS: The number of trials and participants is insufficient to draw final conclusions. A large multicenter study with adequate power is needed.

Follicle Stimulating Hormone↗
PubMed1998

Molecular cloning and expression of rat contraception associated protein 1 (CAP1), a protein putatively involved in fertilization.

Epididymal fluid from rats rendered infertile by oral administration of ornidazole contains a protein CAP1 (contraception-associated protein 1) that is absent from epididymal fluid, but present on epididymal sperm, from fertile vehicle-treated rats. The gene for CAP1 has been isolated from a rat testis cDNA library and its expression investigated in different tissues. The deduced protein sequence of CAP1 contains 189 amino-acid residues and database searches revealed a high degree of homology (83-95%) with human and mouse DJ-1 at the nucleotide and amino acid levels. Northern blot hybridisation from different rat tissues indicated that CAP1 is encoded by a 1.6-kilobase RNA transcript and seems to be ubiquitiously expressed in the rat with a high level of expression in the testis.

Adult↗
PubMedDate not supplied

Natural product extracts that reduce accumulation of the Alzheimer's amyloid beta peptide: selective reduction in A beta42.

Alzheimer's disease (AD) is the most common form of dementia in the elderly. Without a treatment that significantly delays the progression of the disease over 14 million Americans are likely to be affected with AD by the middle of the 21st Century, presenting an enormous economic and social burden. Evidence gathered over the last two decades has implicated the abnormal accumulation of A beta, in particular the longer more amyloidogenic form A beta42, as a potential causative agent in the disease. To screen for compounds that reduce A beta accumulation we have established several high throughput, cell based screens capable of the sensitive and selective detection of A beta40 and A beta42. Using these screens we have analyzed a proprietary library of natural product extracts for their ability to influence A beta accumulation. Using this approach, we have identified several agents capable of influencing total A beta concentration. In addition, we have identified one extract that selectively reduces A beta42. Intracerebroventricular administration of this agent to mice results in a selective reduction in A beta42 in the brain.

Alzheimer Disease↗
PubMed2001

Identification of a nonpeptide ligand that releases bioactive insulin-like growth factor-I from its binding protein complex.

Insulin-like growth factor-I (IGF-I) has both metabolic and mitogenic activities mediated through interaction with the type 1 IGF receptor. The circulation of IGF-I in blood and interstitial fluid is not free but bound mostly to a family of six high affinity IGF-binding proteins, which form stable complexes with IGF and neutralize its bioactivity. Therefore, displacement of this large pool of endogenous IGF from the binding proteins could elevate "free" IGF levels to elicit beneficial effects in diabetes and other IGF-responsive diseases comparable with those produced by administration of exogenous IGF-I. We report here the identification of a nonpeptide ligand NBI-31772, which displaces IGF-I from all six IGF-binding proteins at low nanomolar concentrations from screening of the in-house chemical libraries. Furthermore, the released free IGF-I was shown to be biologically active in an in vitro bioassay. Thus, NBI-31772 could serve as a valuable lead molecule for the design of novel therapeutics to treat diabetes and other IGF-responsive diseases.

Animals↗