Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 93
Filter
1.
Chronobiol Int ; 35(1): 90-100, 2018 01.
Article in English | MEDLINE | ID: mdl-29111816

ABSTRACT

The use of electronic devices with light-emitting screens has increased exponentially in the last decade. As a result, humans are continuously exposed to unintentional artificial light. We explored the effects of acute and chronic exposure to artificial light at night (ALAN) via screen illumination on sleep, circadian rhythms, and related functional outcomes. Nineteen participants (11 female and 8 males, mean age 28.1 ± 7.2 years) underwent a six-night study with three experimental conditions using a repeated-measures design: baseline (first night, no light exposure), acute ALAN exposure (second night), and chronic ALAN exposure (third to sixth nights). Each light exposure lasted for 2 hours (21:00-23:00). Participants underwent an overnight polysomnography at the end of each condition (nights 1, 2, and 6). We collected urine samples (for melatonin metabolite analysis), while body (oral) temperatures were measured before and after exposure. Each morning, the participants filled out questionnaires and conducted a computerized attention test. Both acute and chronic illumination significantly disrupted sleep continuity and architecture and led to greater self-reported daytime sleepiness, negative emotions, and attention difficulties. Both exposure types also altered circadian rhythms, subduing the normal nocturnal decline in body temperature and dampening nocturnal melatonin secretion. In sum, ALAN exposure from electronic screens has an immediate, detrimental, yet stable effect on sleep, circadian regulation, and next-day functional outcomes. Given the widespread use of electronic devices today, our findings suggest that even one night of screen light exposure may be sufficient to cause adverse effects on health and performance.


Subject(s)
Attention/physiology , Circadian Rhythm/physiology , Computers , Lighting , Adolescent , Adult , Body Temperature/physiology , Female , Humans , Light , Male , Melatonin/metabolism , Middle Aged , Photic Stimulation/adverse effects , Sleep/physiology , Young Adult
2.
Chronobiol Int ; 34(7): 855-865, 2017.
Article in English | MEDLINE | ID: mdl-28548897

ABSTRACT

The use of electronic devices with light-emitting screens has increased exponentially in the last decade. As a result, humans are almost continuously exposed to unintentional artificial light. We explored the independent and combined effects of two aspects of screen illumination, light wavelength, and intensity, on sleep, its biological regulation, and related functional outcomes. The 2 × 2 repeated-measure design included two independent variables: screen light intensity (low ([LI] versus high [HI]) and wavelength (short [SWL] versus long [LWL]). Nineteen participants (11F, 8M; mean age 24.3 [±2.8] years) underwent four light conditions, LI/SWL, HI/SWL, LI/LWL, and HI/LWL, in counterbalanced order. Each light exposure lasted for two hours (21:00-23:00), following which participants underwent an overnight polysomnography. On each experimental night, oral temperature and urine samples (for melatonin analysis) were collected at multiple time points. Each morning, participants filled out questionnaires and conducted a computerized attention task. Irrespective of light intensity, SWL illumination significantly disrupted sleep continuity and architecture and led to greater self-reported daytime sleepiness. SWL light also altered biological rhythms, subduing the normal nocturnal decline in body temperature and dampening nocturnal melatonin secretion. Light intensity seemed to independently affect sleep as well, but to a lesser degree. Both light intensity and wavelength negatively affected morning attention. In sum, light wavelength seems to have a greater influence than light intensity on sleep and a wide-range of biological and behavioral functions. Given the widespread use of electronic devices today, our findings suggest that screen light exposure at evening may have detrimental effects on human health and performance.


Subject(s)
Attention/radiation effects , Circadian Rhythm/drug effects , Computers , Light/adverse effects , Sleep Wake Disorders/etiology , Sleep/radiation effects , Adult , Biomarkers/urine , Body Temperature Regulation/radiation effects , Female , Humans , Male , Melatonin/urine , Random Allocation , Risk Assessment , Risk Factors , Sleep Wake Disorders/diagnosis , Sleep Wake Disorders/physiopathology , Time Factors , Young Adult
3.
Article in Spanish | LILACS | ID: biblio-838119

ABSTRACT

El Curriculum Universitario sintetiza una concepción de sujeto junto a una concepción de mundo. Estos se expresan a través del lenguaje, en distintas instancias sociales que se relacionan con (es decir que tienen algún interés en) la Universidad, conformando una red de discursos que coniguran los discursos universitarios o Discursos del Curriculum Universitario. Los objetivos de la investigación se centraron en comprender los modos en que se configuran discursivamente tanto el curriculum universitario como los sujetos que en él se constituyen. Para ello se buscó identificar y describir los conceptos que componen el discurso dominante en el campo académico y analizar el papel que asume la evaluación, dada su capacidad para imponer sentidos así cómo para inducir y modelar prácticas en el campo académico y en general en el ámbito educativo. En el presente trabajo expondremos algunas conclusiones referidas a la posición de los organismos internacionales.


The University Curriculum synthesizes a conception of the subject with a conception of the world. These are expressed through language in different social instances that relate to (ie they have any interest in) the University, forming a network of discourses that shape the university discourses or discourses of University Curriculum. The objectives of the research are focused on understanding the ways in which discursively shape both the university curriculum as subjects who are in it. To do this we sought to identify and describe the concepts that make up the dominant discourse in the academic field and analyze the role assumed by the evaluation, given its ability to impose sense and how to induce and model practices in academia and generally in the field education. In this paper we will discuss some conclusions regarding the position of international organizations.

4.
Pharmacol Biochem Behav ; 92(4): 559-65, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19348837

ABSTRACT

Nearly half of 12th graders have tried marijuana, and 6% use daily. This paper reviews studies on neuropsychological functioning, brain structure, brain function, and subjective and objective measures of sleep in relation to adolescent marijuana use. Adolescents who use marijuana heavily tend to show disadvantaged attention, learning, and processing speed; subtle abnormalities in brain structure; increased activation during cognitive tasks despite intact performance; and compromised objective indicators of sleep quality. Some abnormalities appear to persist beyond a month of abstinence, but may resolve within three months if cessation is maintained. Recommendations for future studies include characterizing these indices in youth prior to the onset of marijuana use then examining change after chronic use has started, and using large samples of youth with varying degrees of involvement with marijuana as well as alcohol, nicotine, and other drugs to characterize the interactive influences on neurocognition and neural health.


Subject(s)
Marijuana Smoking/physiopathology , Marijuana Smoking/psychology , Adolescent , Attention , Brain/pathology , Brain/physiopathology , Cognition , Dyssomnias/etiology , Dyssomnias/physiopathology , Dyssomnias/psychology , Humans , Learning , Marijuana Smoking/pathology , Memory , Neuropsychology , Psychology, Adolescent , Risk-Taking , Sleep/physiology
6.
Osteoporos Int ; 19(4): 529-35, 2008 Apr.
Article in English | MEDLINE | ID: mdl-17929072

ABSTRACT

UNLABELLED: Women with osteoporosis on raloxifene were randomized to 1-34hPTH + raloxifene or raloxifene alone for one year. In the PTH + raloxifene group, bone turnover increased 125-584%, spine BMD increased 9.6%, hip BMD increased 1.2-3.6% and radius BMD declined 4.3%. During the follow-up year, on continued raloxifene, BMD declined slightly at all sites except the femoral neck. INTRODUCTION: The influence of prior antiresorptives on response to 1-34PTH and the ability to maintain BMD gains might differ for antiresorptive agents with different potencies. The objectives were to evaluate biochemical and bone density responses to 1-34PTH in patients on prior and ongoing raloxifene and to determine whether raloxifene maintains bone gains. METHODS: Forty-two postmenopausal women with osteoporosis on raloxifene were randomized to raloxifene alone or 1-34PTH daily for 12 months (continuing raloxifene). Women were then followed for 12 months on raloxifene alone. Bone turnover markers and BMD were measured at baseline and at 3, 6, 12, 18 and 24 months. RESULTS: Biochemical indices increased rapidly during PTH treatment with peak increments of 125-584% for the three markers (p<0.001 vs. baseline). After one year of PTH, mean BMD increases were 9.6% for spine, 2.7% for total hip, 3.6% for trochanter (all p<0.005) and 1.2% in femoral neck (NS), while BMD declined 4.3% in the radius (p=0.003). After PTH withdrawal, on continued raloxifene, BMD declined slightly (0.7-2.9% losses; NS) at all sites, except the femoral neck, where BMD increased modestly (p=0.04). At 24 months, spine and femoral neck BMD remained significantly higher than baseline, while radius BMD remained significantly lower (all p<0.04). CONCLUSION: Substantial gains in BMD of the spine and hip, but not the radius, are seen with one year of PTH treatment in patients on prior raloxifene. After PTH is discontinued, raloxifene partially maintains PTH-induced BMD gains in the spine and hip.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Bone Density/drug effects , Bone Resorption/drug therapy , Osteoporosis, Postmenopausal/drug therapy , Parathyroid Hormone/therapeutic use , Raloxifene Hydrochloride/therapeutic use , Aged , Bone Density/physiology , Bone Density Conservation Agents/metabolism , Bone Resorption/physiopathology , Female , Follow-Up Studies , Humans , Middle Aged , Osteoporosis, Postmenopausal/physiopathology , Parathyroid Hormone/metabolism , Raloxifene Hydrochloride/metabolism , Treatment Outcome
7.
Osteoporos Int ; 19(5): 673-9, 2008 May.
Article in English | MEDLINE | ID: mdl-17999024

ABSTRACT

UNLABELLED: The impact of calcium and vitamin D intake on bone density and one-year fracture risk was assessed in 76,507 postmenopausal Caucasian women. Adequate calcium with or without vitamin D significantly reduced the odds of osteoporosis but not the risk of fracture in these Caucasian women. INTRODUCTION: Calcium and vitamin D intake may be important for bone health; however, studies have produced mixed results. METHODS: The impact of calcium and vitamin D intake on bone mineral density (BMD) and one-year fracture incidence was assessed in 76,507 postmenopausal Caucasian women who completed a dietary questionnaire that included childhood, adult, and current consumption of dairy products. Current vitamin D intake was calculated from milk, fish, supplements and sunlight exposure. BMD was measured at the forearm, finger or heel. Approximately 3 years later, 36,209 participants returned a questionnaire about new fractures. The impact of calcium and vitamin D on risk of osteoporosis and fracture was evaluated by logistic regression adjusted for multiple covariates. RESULTS: Higher lifetime calcium intake was associated with reduced odds of osteoporosis (peripheral BMD T-score < or =-2.5; OR = 0.80; 95% CI 0.72, 0.88), as was a higher current calcium (OR = 0.75; (0.68, 0.82)) or vitamin D intake (OR = 0.73; 95% CI 0.0.66, 0.81). Women reported 2,205 new osteoporosis-related fractures. The 3-year risk of any fracture combined or separately was not associated with intake of calcium or vitamin D. CONCLUSIONS: Thus, higher calcium and vitamin D intakes significantly reduced the odds of osteoporosis but not the 3-year risk of fracture in these Caucasian women.


Subject(s)
Bone Density/drug effects , Calcium, Dietary/administration & dosage , Fractures, Bone/epidemiology , Osteoporosis, Postmenopausal/epidemiology , Vitamin D/administration & dosage , Vitamins/administration & dosage , Aged , Aged, 80 and over , Diet , Female , Humans , Middle Aged , Risk Factors , Surveys and Questionnaires , Time Factors , United States/epidemiology , White People
8.
Nutr Metab (Lond) ; 3: 14, 2006 Feb 15.
Article in English | MEDLINE | ID: mdl-16480509

ABSTRACT

The determinants of bone mineral density (BMD) at multiple sites were examined in a fit college population. Subjects were 755 males (mean age = 18.7 years) entering the United States Military Academy. A questionnaire assessed exercise frequency and milk, caffeine, and alcohol consumption and tobacco use. Academy staff measured height, weight, and fitness. Calcaneal BMD was measured by peripheral dual-energy x-ray absorptiometry (pDXA). Peripheral-quantitative computed tomography (pQCT) was used to measure tibial mineral content, circumference and cortical thickness. Spine and hip BMD were measured by DXA in a subset (n = 159). Mean BMD at all sites was approximately one standard deviation above young normal (p < 0.05). African Americans had significantly higher hip, spine and heel BMD and greater tibial mineral content and cortical thickness than Caucasians and Asians. In Caucasians (n = 653), weight was a significant determinant of BMD at every skeletal site. Prior exercise levels and milk intake positively related to bone density and size, while caffeine had a negative impact. There was an apparent interaction between milk and exercise in BMD at the heel, spine, hip and tibial mineral content and cortical thickness. Our data confirm the importance of race, body size, milk intake and duration of weekly exercise as determinants of BMD and bone size.

9.
Thromb Res ; 116(1): 1-13, 2005.
Article in English | MEDLINE | ID: mdl-15850603

ABSTRACT

INTRODUCTION: Estrogen therapy (ET), tamoxifen and raloxifene are associated with a two- to three-fold increased risk of venous thrombosis (VT); however, the mechanisms by which each drug increases venous thrombosis propensity are not fully understood. The objectives of this investigation were to compare the effects of these three treatments on hemostasis in a head to head randomized placebo-controlled trial. PATIENTS/METHODS: Ninety-four postmenopausal women were assigned to receive oral estrogen (conjugated equine estrogen [CEE] 0.625 mg, n=23), tamoxifen 20 mg (n=24), raloxifene 60 mg (n=24) or placebo (n=23) daily for 6 months. Blood samples were analyzed for procoagulant factors (prothrombin, factors VII [fVII], VIII [fVIII], IX [fIX] and XI [fXI], D-dimer and von Willebrand factor [vWf]), anticoagulant factors (antithrombin [AT], total and free protein S, protein C and activated protein C [APC] resistance) and fibrinolytic factors (thrombin activatable fibrinolysis inhibitor [TAFI] and plasminogen activator inhibitor-1 [PAI-1]), at baseline and at 6 months of treatment. RESULTS: Estrogen increased factor VII and D-dimer, and decreased antithrombin, total and free protein S and PAI-1. Changes with tamoxifen were distinct from estrogen with increases in factors VIII, IX, vWf and free protein S, and decreases in AT, total protein S, protein C and plasminogen activator inhibitor-1. Raloxifene produced similar effects as tamoxifen, but did not increase factor IX or decrease protein C. CONCLUSIONS: Estrogen, tamoxifen and raloxifene affected hemostasis favoring procoagulation and impairing anticoagulation. The biochemical effects of the selective estrogen receptor modulators (SERMs) were distinct from those of estrogen and differed only subtly from each other.


Subject(s)
Estrogens/pharmacology , Hemostasis/drug effects , Raloxifene Hydrochloride/pharmacology , Tamoxifen/pharmacology , Biomarkers/blood , Blood Coagulation Factor Inhibitors/analysis , Blood Coagulation Factors/analysis , Estrogens/administration & dosage , Female , Fibrinolysis/drug effects , Hormone Replacement Therapy/adverse effects , Humans , Postmenopause , Raloxifene Hydrochloride/administration & dosage , Selective Estrogen Receptor Modulators/pharmacology , Tamoxifen/administration & dosage , Thrombophilia/chemically induced
10.
Mol Reprod Dev ; 60(4): 507-16, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11746962

ABSTRACT

It has recently been reported that in human sperm cells, the centromeres are clustered in a chromocenter in the interior region of the nucleus. The aim of the present study was to determine the intra-chromocenter organization of the five centromeres of the acrocentric chromosomes responsible for the biosynthesis of rRNA. The acrocentric centromeres were labeled by fluorescence in situ hybridization (FISH) after mild decondensation of the sperm nuclei to preserve the tail structure. The tail was used as a topographical marker for the orientation of the nucleus. The following results were obtained: (a) the association among the five centromeres was higher than expected from random distribution; (b) all the centromeres observed were randomly located within the chromocenter, occupying about 87% of the total area of the internal nucleus; (c) a major subpopulation of centromeres was located in a preferred area occupying 8.3% of the total nuclear area, with a peak 0.6 microm on the lateral axis and 1.0 microm on the apical side of the longitudinal axis; and (d) The dispersion of the centromeres was not influenced by the degree of the nuclear decondensation. We conclude that in human sperm nuclei, the acrocentric centromeres are organized within a nonlocalized structural element in the chromocenter. The chromocenter can range from an expanded size of 87% of the whole nucleus to a preferred size of 8.3% independent of the degree of nuclear decondensation. These findings have important implications for nuclear function (rRNA) that is not directly related to sperm cell function or early embryo development.


Subject(s)
Cell Nucleus/metabolism , Centromere/metabolism , Spermatozoa/cytology , Cell Nucleus/genetics , Centromere/genetics , Chi-Square Distribution , DNA Probes/metabolism , Humans , In Situ Hybridization, Fluorescence , Male , RNA, Ribosomal/metabolism
11.
J Am Chem Soc ; 123(43): 10738-9, 2001 Oct 31.
Article in English | MEDLINE | ID: mdl-11674007
12.
Sleep Med ; 2(6): 511-6, 2001 Nov.
Article in English | MEDLINE | ID: mdl-14592266

ABSTRACT

OBJECTIVE: The current study was designed to determine whether, with increasing age, sleep apnea improves, becomes worse, or stays the same. BACKGROUND: There is a high prevalence of sleep disordered breathing (SDB) in older adults, but little is known about longitudinal changes. This study followed older adults to examine the natural history of SDB. METHODS: Subjects were randomly selected community-dwelling elderly (n=427). A subset of subjects was studied approximately every 2 years over an 18-year period. Overnight sleep recordings and sleep questionnaires were completed at each time point. RESULTS: Multiple linear regression showed that three variables were associated with change in respiratory disturbance index (RDI):body mass index (BMI) at initial visit (P=0.001), change in BMI (P=0.02), and a consistent self-report of high blood pressure (P=0.005). RDI increase was associated with BMI increase and presence of self-reported high blood pressure. CONCLUSIONS: The changes in RDI that occurred were associated only with changes in BMI and were independent of age. This underscores the importance of managing weight for older adults, particularly those with hypertension.

13.
J Am Geriatr Soc ; 49(12): 1622-7, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11843994

ABSTRACT

OBJECTIVES: Sleep disordered breathing (SDB) is very common in older people and is known to be associated with complaints of impaired daily functioning, including excessive daytime sleepiness and cognitive impairments. As part of a larger study on SDB and aging, it became possible to examine the relationship between SDB and cognition in older men and women. DESIGN: A population-based longitudinal study. SETTING: In-home interviews and home sleep recordings in the greater San Diego area. PARTICIPANTS: Community-dwelling people age 65 and older with high risk for SDB were originally studied from 1981 through 1985 and then followed every 2 years. Data from the 46 subjects who completed Visit 3 and Visit 4 are presented. MEASUREMENTS: Subjects were interviewed in the home about their sleep and medical condition before each visit. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Daytime sleepiness was based on self-report. Objective sleep was recorded in the home and scored for sleep, apneas and hypopneas, and oximetry variables. RESULTS: Increases in respiratory disturbance index (RDI) (P= .036) and increases in daytime sleepiness (P= .002) were associated with decreases in cognitive performance (i.e., increases in cognitive impairment). Increases in RDI were also associated with increases in daytime sleepiness (P= .012). Change in MMSE scores was therefore regressed onto changes in RDI, daytime sleepiness, age, and education, resulting in decreases in MMSE scores being associated with increases in daytime sleepiness (P= .019) but not with changes in RDI (P= .515). There was no significant relationship between changes in oxygen saturation levels and changes in MMSE. CONCLUSIONS: The results of this study suggest that declining cognitive function is associated primarily with increases in daytime sleepiness. Although cognitive decline was also associated with increases in RDI, this association did not hold in the more inclusive model which also included variable of SDB, oximetry, sleep and subjective report. One theoretical model could suggest that any relationship between SDB and cognitive function may be mediated by the effect of SDB on daytime sleepiness. These results suggest that older patients suffering from mild to moderate SDB may benefit from the treatment of SDB, even if they are not markedly hypoxemic.


Subject(s)
Aging/physiology , Cognition Disorders/etiology , Sleep Apnea Syndromes/complications , Aged , Aged, 80 and over , Cognition Disorders/physiopathology , Female , Humans , Interviews as Topic , Longitudinal Studies , Male , Oximetry , Prospective Studies , Psychiatric Status Rating Scales , Random Allocation , Regression Analysis , Residence Characteristics , Sleep Apnea Syndromes/physiopathology , Time Factors
14.
Sleep ; 22(7): 891-8, 1999 Nov 01.
Article in English | MEDLINE | ID: mdl-10566907

ABSTRACT

The purpose of this study was to investigate the relationship between core body temperature and sleep in older female insomniacs and changes in that relationship as a result of passive body heating (PBH). An increase in body temperature early in the evening by way of PBH in older female insomniacs increased SWS in the early part of the sleep period and improved sleep continuity. Fourteen older female insomniacs (60-73 years old) participated in at least two consecutive nights of PBH involving hot (40-40.5 degrees C) baths 1.5-2 hours before bedtime. Hot baths resulted in a significant delay in the phase of the core body temperature rhythm compared to baseline nights. This delay in temperature phase paralleled the improvements in sleep quality.


Subject(s)
Aging/physiology , Body Temperature Regulation/physiology , Body Temperature/physiology , Sleep Initiation and Maintenance Disorders/diagnosis , Sleep, REM/physiology , Adult , Age Factors , Chronic Disease , Circadian Rhythm/physiology , Female , Humans , Middle Aged , Time Factors , Wakefulness/physiology
15.
Mol Psychiatry ; 2(3): 251-4, 1997 May.
Article in English | MEDLINE | ID: mdl-9152990

ABSTRACT

Only in the past decade has a role of heredity in substance abuse been established as a result of extensive twin and family studies. More recently, several candidate genes have been investigated for their possible role in alcoholism and cocaine abuse. Specific genetic factors in opioid substance abuse have not been investigated in man, although animal studies suggest that quantitative trait loci (QTLs) can be identified that predispose mice both to morphine and alcohol preference. Central dopaminergic pathways figure prominently in drug-mediated reinforcement suggesting that dopamine receptors are likely candiadates for association with substance abuse in man. In addition, we recently reported an association between a human personality trait, Novelty Seeking and the long alleles (represented chiefly by the 7-repeat) of the D4 dopamine receptor (D4DR) exon III polymorphism. The personality trait of Novelty Seeking is also more pronounced in substance abusers, who score higher in this dimension than control subjects. The twin role of dopamine receptors in mediating Novelty Seeking and drugreinforcement prompted us to examine a group of Israeli heroin addicts for prevalence of the D4DR repeat polymorphism. We now show that the 7-repeat allele is significantly over-represented in the opioid-dependent cohort and confers a relative risk of 2.46. To our knowledge this is the first report of an association between a specific genetic polymorphism and opioid addiction.


Subject(s)
Exons/genetics , Narcotics/pharmacology , Receptors, Dopamine D2/genetics , Substance-Related Disorders/genetics , Adult , Alleles , Animals , Humans , Male , Mice , Receptors, Dopamine D4
16.
Blood ; 90(12): 4918-23, 1997 Dec 15.
Article in English | MEDLINE | ID: mdl-9389709

ABSTRACT

We previously reported that the abl promoter (Pa) undergoes de novo DNA methylation in the course of chronic myelocytic leukemia (CML). The clinical implications of this finding are the subject of the present study in which samples of CML patients, including a group treated with interferon alpha (IFNalpha) were surveyed. The methylation status of the abl promoter was monitored by polymerase chain reaction (PCR) amplification of the Pa region after digestion with several site-methylation sensitive restriction enzymes. Some 74% of the DNA samples from blood and marrow drawn in the chronic phase were nonmethylated, similar to control samples from non-CML patients. The remaining 26% were partially methylated in the abl Pa region. The latter samples were derived from patients who were indistinguishable from the others on the basis of clinical presentation. Methylated samples were mostly derived from patients known to have a disease of longer duration (26 months v 7.5 months, P = .01). Samples of 30 IFNalpha-treated patients were sequentially analyzed in the course of treatment. Fifteen patients with no evidence of Pa methylation before treatment remained methylation-free. The remainder, who displayed Pa methylation before treatment, reverted to the methylation-free status. The outcome is attributed to IFNalpha therapy, as the Pa methylation status was not reversed in any of the patients treated with hydroxyurea. Methylation of the abl promoter indicates a disease of long-standing, most likely associated with a higher probability of imminent blastic transformation. It appears to predict the outcome of IFNalpha therapy far better than the cytogenetic response.


Subject(s)
DNA Methylation , Genes, abl , Interferon-alpha/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Adolescent , Adult , Aged , Child , Female , Follow-Up Studies , Humans , Hydroxyurea/pharmacology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Male , Middle Aged , Promoter Regions, Genetic
17.
Gen Pharmacol ; 27(7): 1241-6, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8981075

ABSTRACT

1. The effects of carbamylcholine (CaCh) (acetylcholine agonist) and pyridostigmine (Pyr) (acetylcholinesterase inhibitor), on the activity of cytoskeleton-bound and cytosolic phosphofructokinase (PFK), the rate-limiting enzyme in glycolysis, and ATP levels, were studied in rat tibialis anterior (TA) muscle, heart, and brain. 2. In the TA muscle, a marked (about three-fold) increase in the allosteric activity of cytosolic (soluble) PFK was found, 3-5 min following the injection of CaCh or Pyr. The intracellular distribution of the enzyme was not affected by both drugs. Stimulation of glycolysis in this muscle was also expressed by a significant increase in the concentrations of glycolytic intermediates and lactate. Glucose 1,6-bisphosphate (Glc-1,6-P2) levels were unchanged, whereas fructose-2,6-bisphosphate (Fru-2,6-P2) was increased. Glycogenolysis was also stimulated, as deduced from the decrease in glycogen content. The stimulation of glycolysis, induced by both drugs, was accompanied by an increase in ATP level in the TA muscle. 3. In contrast to the stimulatory action of CaCh or Pyr on glycolysis in the TA muscle, both drugs had no effect on cytosolic and cytoskeletal PFK in heart and brain. However, ATP content in both heart and brain was markedly reduced by these drugs, most probably due to their reported harmful effects on mitochondrial function, leading to tissue damage. 4. Electron microscopic studies of TA muscle and heart from rats treated with CaCh or Pyr, revealed severe damage of heart but no harmful effects on TA muscle, which is a muscle with high glycolytic and low oxidative capacity. The present experiments suggest that the accelerated glycolysis in this muscle induced by both drugs, supplies ATP, thus preventing muscle damage.


Subject(s)
Adenosine Triphosphate/metabolism , Carbachol/pharmacology , Cytoskeleton/metabolism , Cytosol/enzymology , Parasympathomimetics/pharmacology , Phosphofructokinase-1/metabolism , Pyridostigmine Bromide/pharmacology , Animals , Brain/drug effects , Brain/enzymology , Cytoskeleton/drug effects , Cytosol/drug effects , Glycogen/metabolism , Glycolysis/drug effects , Heart/drug effects , Lactic Acid/metabolism , Muscle, Skeletal/drug effects , Muscle, Skeletal/enzymology , Muscle, Skeletal/ultrastructure , Myocardium/enzymology , Myocardium/ultrastructure , Rats
18.
Eur Heart J ; 17(10): 1532-7, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8909910

ABSTRACT

UNLABELLED: OBJECTIVE, DESIGN AND PATIENTS: Between August 1981 and July 1983, 5839 consecutive myocardial infarction patients were hospitalized in 13 coronary care units in Israel. The present study examines 10 year survival among 4037 consecutive patients with a first myocardial infarction with either Q or non-Q waves. Demographic and medical data were collected from hospital records, and 1 year clinical follow-up was complete for 99% of hospital survivors. Mortality follow-up was extended to June 1992 (mean 10 years of follow-up). RESULTS: Five hundred and eighty patients (14%) had first myocardial infarctions of the non-Q wave type and 3457 of the Q wave type. Hospital mortality was significantly higher in patients with a Q wave (10%) than those with a non-Q wave myocardial infarction (7%) (P < 0.05). One year post-discharge, non-fatal reinfarction and mortality rates were comparable in patients with Q wave (4% and 7%) and non-Q wave myocardial infarctions (4% and 7% respectively). Similarly, 5 to 10 year post-discharge mortality rates were equally high in patients with a non-Q wave (26% and 44%) as in those with a first episode of a Q wave myocardial infarction (22% and 40% respectively). CONCLUSIONS: Patients with a first non-Q wave acute myocardial infarction exhibited relatively better in-hospital survival than counterparts with a first Q wave infarction, but the advantage did not persist after discharge. Patients with a non-Q wave infarction deserve particular attention as their post-discharge mortality risk is similar to counterparts with a first Q wave myocardial infarction.


Subject(s)
Electrocardiography , Myocardial Infarction/mortality , Aged , Female , Hospital Mortality , Humans , Israel/epidemiology , Male , Middle Aged , Myocardial Infarction/classification , Myocardial Infarction/diagnosis , Prognosis , Recurrence , Survival Rate
19.
Biochem Mol Med ; 56(2): 94-8, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8825070

ABSTRACT

We investigated the regulatory mechanisms which may account for the reduction of glycolysis in brain during severe hypoglycemia. Phosphofructokinase (PFK), the rate-limiting enzyme in glycolysis, is known to be regulated by allosteric effectors, as well as by a reversible binding to cell cytoskeleton. These two mechanisms were studied, in rat brain, during insulin-induced hypoglycemia. Our experiments revealed that the intracellular distribution of PFK was not changed during severe hypoglycemia. However, the allosteric activity of the enzyme (assayed under conditions in which it is sensitive to allosteric effectors) from both the cytosolic (soluble) and cytoskeletal fractions, was significantly reduced. This reduction may be attributed to the marked fall in the level of glucose 1,6-bisphosphate (Glc-1,6-P2), the potent allosteric activator of PFK, as well as to the more moderate decrease in fructose 2,6-bisphosphate and the decrease in fructose 1,6-bisphosphate (the product and allosteric activator of the enzyme). In contrast to our previous findings in muscle, the cytoskeleton-bound PFK from brain was found to be sensitive to allosteric effectors like the soluble enzyme. This may explain the reduction in the allosteric activity of PFK in both the cytosolic and cytoskeletal fractions from brain. The decline in cytoskeleton-bound and cytosolic PFK activity, induced by the fall in its allosteric activators, may lead to the reduction in brain glycolytic rate, which was reflected by the marked decrease in lactate content during hypoglycemia.


Subject(s)
Brain/metabolism , Glucose-6-Phosphate/analogs & derivatives , Hypoglycemia/chemically induced , Insulin/pharmacology , Phosphofructokinase-1/metabolism , Allosteric Regulation , Animals , Brain/enzymology , Brain/physiopathology , Cytoskeleton/metabolism , Cytosol/enzymology , Glucose-6-Phosphate/metabolism , Rats
20.
J Clin Epidemiol ; 48(10): 1197-205, 1995 Oct.
Article in English | MEDLINE | ID: mdl-7561981

ABSTRACT

The purpose of this study was to assess the predictive value of admission heart rate (HR) for in-hospital and 1 year post-discharge mortality in a large cohort of patients hospitalized for acute myocardial infarction (MI). Data were derived from the SPRINT-2 secondary prevention study population, and included 1044 patients (aged 50-79), hospitalized in 14 coronary care units in Israel with acute MI in the years 1985-1986, before the beginning of thrombolytic therapy in acute MI. Demographic, historical and medical data were collected for each patient. All deaths during initial hospitalization and 1 year post-discharge were recorded. In-hospital mortality was 5.2% for 294 patients with HR < 70 beats/min, 9.5% for 532 patients with HR 70-89 beats/min, and 15.1% for 323 patients with HR > or = 90 beats/min (p < 0.01). One year post-discharge mortality was 4.3% for patients with HR < 70 beats/min, 8.7% for patients with HR 70-80 beats/min and 11.8% for patients with HR > or = 90 beats/min (p < 0.01). An increasing trend of mortality with higher HR was confined to patients with mild CHF (p = 0.02) and likely to patients with absent CHF (p = 0.06), but this post hoc observation requires confirmation in larger groups. The combination of high admission HR (> or = 90 beats/min) and a systolic blood pressure < 120 mmHg was a powerful predictor of in-hospital mortality. Multivariate analysis showed that admission HR was an independent risk factor for in-hospital and 1 year post-discharge mortality.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Heart Rate , Myocardial Infarction/mortality , Myocardial Infarction/physiopathology , Patient Admission , Aged , Diabetes Complications , Female , Follow-Up Studies , Heart Failure/complications , Hospital Mortality , Humans , Male , Middle Aged , Multivariate Analysis , Myocardial Infarction/complications , Predictive Value of Tests , Prognosis , Risk Factors
SELECTION OF CITATIONS
SEARCH DETAIL
...