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PubMedDate not supplied

Pancreatic beta-cell death, regeneration and insulin secretion: roles of poly(ADP-ribose) polymerase and cyclic ADP-ribose.

In the early 1980s, we proposed a unifying model for beta-cell damage (The OKAMOTO model), in which poly(ADP-ribose) synthetase/polymerase (PARP) activation plays an essential role in the consumption of NAD+, which leads to energy depletion and necrotic cell death. In 1984, we demonstrated that the administration of PARP inhibitors to 90% depancreatized rats induces islet regeneration. From the regenerating islet-derived cDNA library we isolated Reg (Regenerating Gene) and demonstrated that Reg protein induces beta-cell replication via the Reg receptor and ameliorates experimental diabetes. More recently, we showed that the combined addition of IL-6 and dexamethasone induces the Reg gene expression in beta-cells and that PARP inhibitors enhance the expression. In 1993, we found that cyclic ADP-ribose (cADPR), a product synthesized from NAD+, is a second messenger for intracellular Ca2+ mobilization for insulin secretion by glucose, and proposed a novel mechanism of insulin secretion, the CD38-cADPR signal system. Therefore, PARP inhibitors prevent beta-cell necrosis, induce beta-cell replication and maintain insulin secretion.

Animals↗
PubMed1984

Molecular cloning of hepatic 5-aminolevulinate synthase.

Hepatic 5-aminolevulinate synthase was induced in chick embryos by administration of the porphyrinogenic drugs 2-allyl-2-isopropylacetamide and 3,5-diethoxycarbonyl-1,4-dihydrocollidine. A cDNA library was constructed from drug-induced liver mRNA and clones containing sequences coding for 5-aminolevulinate synthase were identified by hybrid-selected translation. The identity of these clones was confirmed by comparing DNA sequence data with the amino acid sequence of peptides from purified 5-aminolevulinate synthase. From Northern blot analysis the size of the mRNA for 5-aminolevulinate synthase was estimated to be 2800 base pairs, approximately 600 base pairs more than that required to code for the primary translation product of relative molecular mass 74000.

5-Aminolevulinate Synthetase↗
PubMed1993

[President Agustin P. Justo and the Faculty of Medicine: other times].

In January this year it was the 50 anniversary of Gral. Agustin P. Justo death, who was President of Argentine during the period 1932-1938. His presence was remarkable so because of his good administration as for his helping the cultural, scientific and teachers activities. He was the owner of a valuable library where he had lots of books about American History. During his government the "Junta de Historia y Numismática" became the "Academia Nacional de Historia". He admired Gral. Bartolomé Mitre, and he ordered the publication of his complete work, writing the introduction. He acted in a distinguished time, characterized by a high respect for intellectual and scientific hierarchy, and by the professors of the U.B.A., where he gave prestige to several acts with his presence and honoring the laureates.

Argentina↗
PubMed1991

A collaborative institutional model for integrating computer applications in the medical curriculum.

The introduction and promotion of information technology in an established medical curriculum with existing academic and technical support structures poses a number of challenges. The UNC School of Medicine has developed the Taskforce on Educational Applications in Medicine (TEAM), to coordinate this effort. TEAM works as a confederation of existing research and support units with interests in computers and education, along with a core of interested faculty with curricular responsibilities. Constituent units of the TEAM confederation include the medical center library, medical television studios, basic science teaching laboratories, educational development office, microcomputer and network support groups, academic affairs administration, and a subset of course directors and teaching faculty. Among our efforts have been the establishment of (1) a mini-grant program to support faculty initiated development and implementation of computer applications in the curriculum, (2) a symposium series with visiting speakers to acquaint faculty with current developments in medical informatics and related curricular efforts at other institution, (3) 20 computer workstations located in the multipurpose teaching labs where first and second year students do much of their academic work, (4) a demonstration center for evaluation of courseware and technologically advanced delivery systems. The student workstations provide convenient access to electronic mail, University schedules and calendars, the CoSy computer conferencing system, and several software applications integral to their courses in pathology, histology, microbiology, biochemistry, and neurobiology. The progress achieved toward the primary goal has modestly exceeded our initial expectations, while the collegiality and interest expressed toward TEAM activities in the local environment stand as empirical measures of the success of the concept.

Academic Medical Centers↗
PubMed1996

Use of large databases for resolving critical care problems.

Large databases allow for rapid access to large volumes of data. To convert raw data to information, large numbers of data points must be correlated into a descriptive pattern that can be interpreted by the user. Databases must be constructed so as to allow reliable extraction of the raw data into a format that supports analysis of events in a meaningful, objective, and reproducible manner. Databases must be responsive to a variety of users. They must not demand unrealistic amounts of effort on those responsible for data entry. Standard protocols in various stages of development will make databases easier to use and more reliable. Database management tools such as the Internet and the National Library of Medicine will become more integrated into the practice of critical care medicine at all levels, including administration, clinical care, and research. This article provides an overview of the capabilities and difficulties associated with large databases. The major areas of use of large databases in the hospital setting are administration, bibliographic, patient care, research, and education. Each of these areas has different requirements and is supported by different types of databases. The advantages and disadvantages of linear, relational, and object-oriented databases are discussed. Issues relating to methods of data entry and the accuracy and reliability of data are discussed. The challenges involving integration of various sources of data and the interfacing of devices are reviewed.

Critical Care↗
PubMedDate not supplied

[Fom orphan receptor to novel neuropeptide: an example of reverse pharmacology].

Nociceptin, a neuropeptide 17 amino acid residues in length, is the first novel bioactive substance to have been discovered by functional genomics. Nociceptin was isolated from a rat brain extract as the endogenous ligand to an orphan receptor, ORL1 (Opioid Receptor-Like 1), structurally akin to opioid receptors, whose cDNA had been cloned from a human brain stem library. The peptide is processed from a larger precursor polypeptide, prepro-nociceptin, which is widely distributed in the nervous system. Nociceptin is primarily an inhibitory neuropeptide that acts on neurons to depress synaptic transmission. Nociceptin's wide spectrum of pharmacological actions hints at several potential therapeutic applications for ORL1 receptor agonists and/or antagonists, particularly for treating pain states, stress and anxiety, cognitive defects, and drug addiction. A major challenge is now the discovery and pharmacological in vivo profiling of ORL1 receptor ligands that are active by medically practical routes of administration.

Amino Acid Sequence↗
PubMed1997

Pharmacokinetic analysis of mizolastine in healthy young volunteers after single oral and intravenous doses: noncompartmental approach and compartmental modeling.

This paper presents the analysis of the kinetics of a new antihistamine, mizolastine, in 18 healthy volunteers, from concentrations measured after an intravenous infusion and two different oral administrations: tablet and capsule. Two approaches were used to analyze these data: (i) a noncompartmental approach implemented in PHARM-NCA; (ii) a compartmental modeling approach implemented in a new S-PLUS library, NLS2, which allows the estimation of variance parameters simultaneously with the kinetic parameters. For the compartmental modeling approach, two-compartment open models were used. According to the Akaike criterion, the best model describing the kinetics of mizolastine after oral administration was the zero-order absorption model. The kinetic parameters obtained with PHARM-NCA and NLS2 were similar. The estimated duration of absorption was greater for the tablets than for the capsules (with means equal to 1.13 hr and 0.84 hr respectively). After an intravenous infusion, the mean estimated clearance was 4.9 L/hr, the mean lambda 2-phase apparent volume of distribution was 89.6 L and the mean terminal half-life was 12.9 hr.

Administration, Oral↗
PubMed2026

Effects of antidepressant administration on physical performance and perceived exertion in athletes: systematic review and meta-analysis.

INTRODUCTION: Antidepressants are commonly prescribed in athletes with depressive disorders, yet their potential effects on physical performance and perceived exertion remain unclear, and existing evidence is limited and inconsistent. AIM: This systematic review and meta-analysis aimed to evaluate the effects of antidepressant use on objective physical performance and perceived exertion in athletes. METHOD: A systematic literature search was conducted in PubMed, the Cochrane Library, Web of Science, and SPORTDiscus through March 2025. Eligible studies were randomised controlled trials (RCTs) published in English that enrolled elite, competitive, or recreational athletes; compared antidepressant administration with placebo or no treatment; and reported at least one objective or subjective performance-related outcome. Meta-analyses were performed using random-effects models, and pooled mean differences with 95% confidence intervals (CI) were calculated. This systematic review and meta-analysis was registered in PROSPERO (CRD420251123740). RESULTS: Ten crossover RCTs involving 99 male athletes were included. Interventions included a norepinephrine reuptake inhibitor (reboxetine), a norepinephrine-dopamine reuptake inhibitor (bupropion), and selective serotonin reuptake inhibitors (fluoxetine or paroxetine). Acute antidepressant administration was associated with a small increase in rating of perceived exertion (RPE; mean difference 0.52 points on the Borg 6-20 scale, 95% CI 0.01-1.04; p&#x2009;<&#x2009;0.05). No significant overall effects were observed for time-trial performance, mean power output, heart rate or blood lactate. However, subgroup analyses showed that reboxetine significantly impaired time-trial performance (mean difference 3.62&#xa0;min, 95% CI 0.18-7.06; p&#x2009;<&#x2009;0.05) and reduced mean power output (mean difference&#x2009;-&#x2009;19.97 W, 95% CI&#x2009;-&#x2009;36.87 to&#x2009;-&#x2009;3.06; p&#x2009;<&#x2009;0.05). CONCLUSION: Short-term antidepressant administration in athletes was associated with a small increase in perceived exertion, without consistent impairment in objective physical performance. As the current evidence derives exclusively from male athletes and acute exposure, further research should clarify its relevance to female athletes and to longer-term antidepressant treatment in athletes with depressive disorders.

Humans↗
PubMed2003

Molecular and biochemical characterization of an enzyme responsible for the formation of hypericin in St. John's wort (Hypericum perforatum L.).

A major gene termed Hyp-1 encoding for hypericin (HyH) biosynthesis was cloned and characterized from Hypericum perforatum (St. John's wort) cell cultures. H. perforatum leaves are widely used as an herbal remedy in the treatment of mild to moderate depression. Hypericin, a photosensitive and red-colored naphthodianthrone, has been reported as the bioactive compound responsible for reversing the depression symptoms. In this study a novel red-color-based colony screening method for examining a cDNA library (lambda-TriplEX2) derived from H. perforatum cell cultures revealed the gene responsible for hypericin biosynthesis after the administration of emodin, a precursor of hypericin. The selected clones were expressed in Escherichia coli (BM 25.8 line) and were further screened for biosynthesis of emodin to hypericin, which resulted in an 84.6% conversion. The full-length cDNA sequence of Hyp-1 is 782 nucleotides in length with an open reading frame of 477 nucleotides coding for a protein of 159 amino acids, with a 45.1% homology to Bet.v.1 class allergens. Reverse transcriptase-PCR analysis showed high levels of Hyp-1 transcripts in dark-grown cell cultures compared with the levels in light-grown cell cultures and leaves. Southern blot analysis showed the presence of a single Hyp-1 gene in H. perforatum. Furthermore, Hyp-1 was expressed with a His6 affinity tag linked to its N terminal region using the expression vector pET-28a, and the recombinant Hyp-1 protein was able to convert HyH from emodin under in vitro conditions. HyH product inhibition was observed with emodin analogues, rhein, rhein methyl ester, and DNA3-55-1. Our results demonstrate a direct and complex conversion of emodin to HyH that is solely catalyzed by Hyp-1, a Bet.v.1 class allergen from H. perforatum.

Amino Acid Sequence↗
PubMed1997

[The Hypertension Cochrane Review Group. Presentation and user's guide].

Cochrane collaboration has been developing since 1992 as an international network aiming at performing systematic reviews of available data on therapeutic effectiveness. The fundamental principles of this organisation are trying to avoid duplication of efforts, seeking the best reliability, using reproducible and quantitative synthesis techniques, offering constantly updated results. All health domains are progressively covered. The production unit in one domain is the review group. The Hypertension Cochrane Review Group (HTN CRG) has been officially registered on May 15th 1996. Information and products from the group are available through its news letter, through the Cochrane Library CD-ROM, regularly updated, and on the Internet (http://merece.uthscsa.edu/htncrg). The Hypertension Cochrane Review Group includes an editorial board (with an administrator and three editors), the authors of systematic reviews, internal and external reviewers. The geographic link is the San Antonio Cochrane Centre (Texas, USA). Invitations to participate have been sent to people interested in hypertension and who where known to the Cochrane collaboration, and to authors of previous reviews in hypertension. It is possible to collaborate with the HTN CRG through: performing a systematic review; reviewing protocols and systematic reviews; hand-searching medical journals; being a member of the editorial team. The first protocol for a systematic review edited by the group concerns antihypertensive treatment in the elderly, and is available in the 1996 and subsequent editions of the Cochrane Library. The group welcomes other reviews from domains awaiting registration, and collaborates with related domains review groups such as Diabetes CRG, or Stroke CRG. The group contributes to the effort of hand-searching medical literature, Pr Plouin being responsible for the Archives des Maladies du Coeur et des Vaisseaux. The second edition in 1996 of the Cochrane Library included 114 systematic reviews and 131 protocols, being the only media with similar objectives.

Computer Communication Networks↗
PubMed1988

Information management through integration of distributed resources.

Duke University Medical Center conducted a strategic planning process focused on information management needs beginning in 1983 and ending in 1985. That effort concluded that the institution was ready to establish an Integrated Academic Information Management System (IAIMS). A model was proposed in which information management was to be achieved through integrated distributed resources. The elements of the IAIMS model are ongoing policy development and planning; communications; an electronic library or resource inventory; coordination of the development or selection of the end-user function; user support; and ongoing evaluation. This model is being tested to determine its effectiveness in meeting the administrative, patient care, research, and educational needs of a basic science department and a clinical science department at Duke University.

Academic Medical Centers↗
PubMed1987

A PC-based free text retrieval system for health care providers. Design and development.

The purpose of this paper is to describe the design and development of the Clinical Practice Library of Medicine (CPLM). CPLM is an investigational project aimed at providing health care practitioners with critical in-depth information similar to that obtained from a medical reference library or consultant. When used in conjunction with the physician's knowledge, CPLM can provide valuable diagnostic prompting information to assist in rapidly reaching a suitable diagnosis for timely administration of appropriate treatment. This system may also be used to assist paramedical professionals working in remote areas where other expert medical assistance may not be available.

Computer Systems↗
PubMed1998

Web-based resources for retrieving health policy information: NLM and beyond.

This paper identifies Web-based resources of interest to the health policy community. Both information useful for developing health policy and information about existing health policy are included. Resources described are classified into three major categories: traditional and grey literature, statistical and epidemiological data, and legal and legislative material. National Library of Medicine (NLM) resources include MEDLINE, DIRLINE, HealthSTAR, HSRProj, and HSTAT. In addition, NLM's National Information Center on Health Services Research and Health Care Technology (NICHSR) has a Web page (http:/(/)www.nlm.nih.gov/nichsr/nichsr.++ +html) that provides an extensive listing of health-policy-related Web sites. Some of the other resources highlighted include those available from the Health Care Financing Administration (HCFA), the National Center for Health Statistics (NCHS) of the Centers for Disease Control and Prevention (CDC), the National Committee for Vital and Health Statistics (NCVHS), and the Library of Congress.

Health Policy↗
PubMed1990

A medical information networking system between practitioners and academia.

This paper reports on a one-year experience with an information networking system (MIS) between 47 rural practitioners and an academic center. Physicians were invited to phone in non-emergency clinical questions specific to daily practice needs to a telephone answering service located in the medical school library. Two-hundred-forty questions triggered by patient visits, colleagues, local rounds, allied health or local professionals, and on-site administrative meetings were forwarded to the MIS. All inquiries were classified according to the International Classification of Disease-9th Revision-Clinical Modification, and categorized into three areas of practice: diagnostic/investigative, general treatment, and pharmacology (therapeutics). The paper outlines how specific practice questions are being screened and adopted for decisions relating to four current activities which assist the ongoing maintenance of competence: 1) CME program planning, 2) residency/undergraduate curriculum development, 3) individualized CME for specific practitioners and sites, and 4) future CME research. The physician inquiries represent true needs in rural medical practice and as such should be given high priority in programs and assessments addressing the maintenance of competence.

Academic Medical Centers↗
PubMed2000

Prophylactic doxapram for the prevention of morbidity and mortality in preterm infants undergoing endotracheal extubation.

BACKGROUND: When preterm infants have been given intermittent positive pressure ventilation (IPPV) for respiratory failure, weaning from support and tracheal extubation may be difficult. A significant contributing factor is thought to be the relatively poor respiratory effort and tendency to develop hypoventilation and apnea, particularly in very preterm infants. Doxapram stimulates breathing and appears to act via stimulation of both the peripheral chemoreceptors and the central nervous system. This effect might increase the chance of successful tracheal extubation. OBJECTIVES: In preterm infants being weaned from IPPV and in whom endotracheal extubation is planned, does treatment with doxapram reduce the use of intubation and IPPV, or reduce other morbidity, without clinically important side effects? In this regard, how does doxapram compare with standard treatment or with an alternative treatment such as methylxanthine or CPAP? Subgroup analyses were prespecified according to birth weight and/or gestational age, use of co-interventions (methylxanthines or nasal CPAP), and route of administration (intravenous or oral). SEARCH STRATEGY: The standard search strategy of the Neonatal Review Group as outlined in the Cochrane Library was used. This included searches of the Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register, MEDLINE and EMBASE. SELECTION CRITERIA: Eligible studies included published trials utilising random or quasi-random patient allocation in which preterm or low birth weight infants being weaned from IPPV were given doxapram compared with standard care or other treatments, to facilitate weaning from IPPV and endotracheal extubation. Trials were independently assessed by the authors before inclusion. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. Each author extracted data separately; the results were compared and any differences resolved. The data were synthesized using the standard method of Neonatal Review Group with use of relative risk and risk difference. MAIN RESULTS: Two trials involving a total of 85 infants compared doxapram and placebo. In both the individual trials and the meta-analyses there were no significant differences between the doxapram and placebo groups in any of the outcomes (failed extubation, death before discharge, respiratory failure, duration of IPPV, side effects, oxygen at 28 days or oxygen at discharge). There was a trend towards an increase in side effects (hypertension or irritability leading to cessation of treatment) in the doxapram group [summary RR 3.21 (0.53, 19.43). In one of these two trials (Huon 1998) an 'alarming rise in blood pressure' occurred in five infants in the doxapram group and none of the controls, although in only one was treatment withdrawn. One additional trial involving only eight infants compared doxapram with aminophylline, but there were insufficient data for meaningful analysis. REVIEWER'S CONCLUSIONS: The evidence does not support the routine use of doxapram to assist endotracheal extubation in preterm infants who are eligible for methylxanthine and/or CPAP. The results should be interpreted with caution because the small number of infants studied does not allow reliable assessment of the benefits and harms of doxapram. Further trials are required to evaluate the benefits and harms of doxapram compared with no treatment or with other treatments, such as methylxanthines or CPAP, to evaluate whether it is more effective in infants not responding to these other treatments, and to assess whether the drug is effective when given orally.

Doxapram↗
PubMed1990

Expression of reg protein in rat regenerating islets and its co-localization with insulin in the beta cell secretory granules.

Regenerating islets can be induced by the administration of poly(ADP-ribose) synthetase inhibitors to 90% depancreatized rats. In screening a regenerating islet-derived cDNA library, we previously isolated a novel gene. reg (regenerating gene), which encodes a 165-amino acid protein with a 21-amino acid signal sequence. In the present study, we have examined the expression and localization of reg protein in the regenerating islets by immunocytochemical techniques using a monoclonal antibody against a recombinant rat reg protein of 144 amino acids without the signal sequence. Light microscopy examination showed strong immunoreactivity for reg protein in the regenerating islets of the rats at two weeks and two months after 90% pancreatectomy, whereas reg protein was almost undetectable in normal rat islets or in the islets of the rats one year after the pancreatectomy. Almost all the reg protein-positive cells were stained for insulin. By applying the immunogold technique at the ultrastructural level, it was demonstrated that both reg protein and insulin occur in the central granular core of the regenerating Beta cell secretory granules. These results suggest that reg protein is synthesized in and secreted from the regenerating Beta cells and that its expression is closely associated with Beta-cell regeneration.

Animals↗