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PubMed2002

High persistence of statin use in a Danish population: compliance study 1993-1998.

AIMS: Several studies have found that compliance with lipid-lowering drug (LLD) treatment is low. However, the results of these studies were based on crude measures of compliance. The aim of this study was to describe compliance with statin treatment by analysing prescription patterns on an individual level in a population-based prescription database over a 6 year period. METHODS: For incident statin users, all prescriptions for statins and drugs indicating cardiovascular disease or diabetes were retrieved from the OPED prescription database covering a population of about 470,000 inhabitants. Treatment was considered discontinued if the interval between two prescriptions exceeded number of tablets prescribed, plus 30 days. Compliance was assessed in terms of persistence and continuity. Persistence was defined as the period from the first prescription date to the date of discontinuation. Continuity was defined as the number of days with treatment (=number of tablets) divided by the total number of days in the period of persistence. RESULTS: 11% of the study cohort only received a single statin prescription. Survival analyses revealed a median persistence of 41 months. Less than 15% of the patients had more than 20% days without therapy within the period of persistence. Patients under 45 years without drug indicators of cardiovascular disease or diabetes presented the lowest compliance. CONCLUSIONS: The study showed good compliance with statin treatment in terms of persistence and continuity. A high percentage of the youngest patients, however, seemed to discontinue treatment before obtaining the full benefit in terms of decreased risk of coronary heart morbidity and mortality.

Adolescent↗
PubMed1998

Links between maternal care and persistent infant crying in the early months.

A community sample was screened to select three groups of infants and their mothers according to how much the babies cried at 6 weeks of age, the peak age for infant crying. The three groups--of moderate (n = 55), evening (n = 38) and persistent criers (n = 67) and their mothers--were assessed by diary, observation and questionnaire measures of mother and infant characteristics and interactions at 6 weeks and 5 months of infant age. At 6 weeks, mothers of persistent criers spent more time interacting with and physically stimulating their babies. Below-optimum maternal sensitivity/affection was linked to moderately increased crying in the infants overall. However, most mothers of persistent criers showed optimum sensitivity and affection, while no significant links between maternal sensitivity/affection and infant crying were found in the persistent crying group. By 5 months, when infant crying declined, the range and size of differences between mothers of persistent criers and other mothers declined. Home observations and a standard play measure failed to show group differences in maternal sensitivity, affection and intrusiveness at this age. The findings show that persistent infant crying in the early months often occurs in spite of high quality maternal care, so that in most cases the crying is probably not due to inadequate parenting. The need to distinguish general community cases from those at social or medical risk is emphasized and the findings' implications for professionals are discussed.

Adult↗
PubMed2002

Persistence of Escherichia coli O157:H7 in soil and on plant roots.

Soil microcosms were inoculated with Escherichia coli O157:H7 to test persistence in fallow soil, on roots of cover crops and in presence of manure. In fallow soils, E. coli O157:H7 persisted for 25-41 days, on rye roots for 47-96 days and on alfalfa roots, in a silt loam soil, for 92 days whereas on other legumes persistence ranged from 25-40 days, similar to fallow soil. Manure did not seem to affect the persistence of E. coli O157:H7 in these soils. Indigenous and manure-applied coliform populations often decreased faster when E. coli O157:H7 was applied, indicating possible competition between microflora. Coliform populations in microcosms not inoculated with E. coli O157:H7 decreased more slowly or increased. Microbial community analyses showed little effect for E. coli O157:H7 inoculation or addition of manure. Microbial community metabolic activity was enhanced from rye roots after 14 days and by 63 days from alfalfa roots. Microbial community lactose utilization increased over time on rye roots in all soils and on alfalfa roots in a silt loam soil when E. coli O157:H7 was inoculated. Lactose utilization also increased for uninoculated rye roots, soil around rye roots and in some fallow soils. Our data suggest that clay increases persistence and activity of E. coli O157:H7 and other coliforms. In frozen soil stored for over 500 days, E. coli O157:H7 was viable in 37% of tested samples. In summary, E. coli O157:H7 persisted longer and activity was enhanced with some cover crops in these soils due to plant roots, the presence of clay and freezing.

Aluminum Silicates↗
PubMedDate not supplied

Predictors of long-term persistence on statins in a subsidized clinical population.

OBJECTIVES: The use of statins in primary prevention of cardiovascular disease is currently under debate. This study characterizes and identifies predictors of the persistence of use of statins in a clinical cohort of subsidized new users of similar age to the WOSCOPS trial subjects. METHODS: Medical, pharmaceutical, and demographic records for the period January 1, 1987 through December 31, 1994 were extracted from the databases of Québec's provincial health plan for a 10% random sample of social assistance recipients. Patients remained eligible for inclusion if they had received a first dispensation of a statin between January 1, 1987 and July 31, 1994. Persistence was defined as the number of days on treatment with a statin while continuing to renew dispensations within a defined time limit. RESULTS: New users of statins included 983 social assistance recipients who were observed for a total of 2,439,153 person-days. Median persistence on statin treatment was 173 (95% CI = 155, 204) days. Only 13% of patients persisted for 5 years of treatment. A higher index of chronic morbidity, pre-existing cardiovascular disease, and previous use of nicotinic acid were predictive of longer persistence on statin medication. Those patients whose first statin dispensation was for lovastatin discontinued treatment earlier than those whose first dispensation was for pravastatin or simvastatin. CONCLUSIONS: New users showed low persistence on statins in a cohort of socially assisted persons aged 45-64, in spite of the minimal financial cost of the drug for such beneficiaries of Québec's provincial health plan.

Journal Article↗
PubMed1996

In vitro and in vivo persistence of reticulocytes from donor red cells.

BACKGROUND: Reticulocytes are important in the phenotyping of transfused patients. Reticulocytes can persist in blood units for the shelf life of the unit. STUDY DESIGN AND METHODS: Temperature dependence of reticulocyte persistence was examined in vitro at 4, 24, and 37 degrees C by using thiazole orange staining and flow cytometric analysis. Two-color flow cytometric analysis was used to evaluate the persistence of donor reticulocytes in transfused patients. RESULTS: Flow cytometric analysis using thiazole orange demonstrated that persistence of reticulocytes in units of stored CPDA-1 blood was temperature-dependent. Reticulocytes disappeared over 13 and 6 days at 24 degrees C and 37 degrees C, respectively, but at 4 degrees C the reticulocyte count changed little over 35 days. Two-color flow cytometric analysis of reticulocyte antigens was used to follow donor reticulocytes in 14 transfusion events in nine different patients. Donor reticulocytes persisted through 24 hours in 75 percent of the patients and were detectable at 48 hours in three patients. CONCLUSION: This study demonstrates that reticulocytes persist during refrigerated storage; they are detectable in the circulation of most recipients for the first 24 hours after transfusion and in the circulation of a few recipients after 48 hours. These findings may have relevance for separation techniques based on reticulocyte density in samples drawn shortly after transfusion and for evaluation of reticulocyte counts in patients with hematologic abnormalities.

Blood Donors↗
PubMed2002

Characterization of paroxysmal and persistent atrial fibrillation in the human left atrium during initiation and sustained episodes.

INTRODUCTION: Atrial fibrillation (AF) in the left atrium (LA) is poorly defined in terms of regional differences in the degree of organization, characteristics of paroxysmal and persistent variants, and electrophysiologic events that develop at the onset of episodes. METHODS AND RESULTS: The study population consisted of 21 patients (15 men and 6 women; mean age 58+/-9.4 years) with paroxysmal (10 patients) or persistent (11 patients) AF. Mapping of the LA during sustained episodes and the onset of AF was performed with a 64-electrode basket catheter. At the onset of AF, repetitive beats starting with atrial premature complexes and ending with generation of the earliest fibrillatory activity were defined as intermediary rhythm. Patients with paroxysmal AF had longer AF cycle lengths and more pronounced regional differences than patients with persistent AF. In total, AF cycle lengths in the LA in patients with persistent AF were 20% shorter than in patients with paroxysmal AF. Initiation of AF was preceded by an intermediary rhythm of 5.5+/-2.5 cycles (6.3+/-2.7 cycles in paroxysmal AF vs 4.2+/-1.0 cycles in persistent AF; P = 0.026). At the onset of AF, the earliest generators of fibrillatory activity were located more frequently in the posterior wall of the LA. CONCLUSION: AF in the LA displays substantial regional differences in terms of AF cycle lengths and degree of organization. Patients with persistent AF have shorter cycle lengths and a higher degree of disorganized activity than patients with paroxysmal AF. Intermediary rhythms play an important role in initiation of AF via activation of generator regions in the LA.

Adult↗
PubMed1994

Relationships between broodiness expression laying persistency and concentrations of hormones during the first productive period in turkey hens (Meleagris gallopavo).

The changes in egg production, in broodiness index and in plasma concentrations of LH, prolactin, oestradiol and progesterone were monitored throughout the first period of laying in turkey hens. The hens were subsequently classified according to their ability to express broodiness (33%) and their laying persistency; 25% were out-of-lay by the end of the experiment. A high percentage (67%) of the hens that went out-of-lay had previously been identified as broody. Altogether, a significant (p < 0.05) physiological stage effect was found when comparing prolactin, oestradiol and progesterone data obtained from short and long laying persistency hens and this stage effect was also significant for oestradiol and progesterone data obtained from broody and non-broody hens. Otherwise, plasma LH concentrations decreased slightly but significantly throughout the laying year in all hens but no significant differences between physiological states were observed, although the decrease was more pronounced in the hens that went out-of-lay. Plasma progesterone concentrations remained stable throughout in laying hens but decreased significantly in broody and/or out-of-lay hens. Plasma prolactin concentrations were maximal between the 5th and 12th week of egg production and the levels observed in laying hens that did not become broody or had a long laying persistency were twice those measured in broody and/or out-of-lay hens. In the meantime, plasma oestradiol concentrations were lower and stable in laying hens, whereas they were higher during the first half of the productive period in broody and short laying persistency hens. These results suggest that, under our experimental conditions, the hormonal profiles of prolactin and oestradiol for a given hen during the first 10 weeks of the laying cycle may provide predictive information for future changes in its physiological status. The inverse relationship that was observed here between high early plasma concentrations of oestradiol and laying persistency is original. In addition, the relationship between the ability to express broodiness and high and low early plasma concentrations of oestradiol and prolactin, respectively, in hens submitted to preventive broody treatment has not been reported previously. Furthermore, it seems clear that high initial concentrations in prolactin, far from exerting any deleterious effects on egg production are closely associated with a longer persistency of egg laying.

Animals↗
PubMed2001

The morbidity, time course and predictive factors for persistent post-thoracotomy pain.

After thoracotomy, patients often suffer from a persistent pain syndrome called post-thoracotomy pain. To elucidate morbidity, time course, and predictive factors for this syndrome, we analyzed follow-up data for 85 post-thoracotomy patients. We used a four-point scale to assess pain: none, slight, moderate and severe. Of 85 patients, 50 reported pain (39 slight, 11 moderate) one day after surgery. A year after surgery, the patients were polled using a simple questionnaire received by the mail. Sixty patients reported persistent pain (34 slight, 14 moderate, 12 severe) a month after surgery, and 35 patients reported persistent pain (33 slight, two moderate) around the time of the poll (1 year after surgery). Although pain deterioration was observed in 40% (34/85) of patients during month 1 after surgery, pain alleviation was seen in 48% (41/85) of patients during months 2-12. Stepwise regression analysis revealed that female gender and pain at postoperative day 1 were predictive for persistent pain both 1 month and 1 year after thoracotomy. Among 35 patients with persistent pain 1 year after surgery, 24 cases reported paresthesia-dysesthesia, and 14 cases reported hypoesthesia. The present data thus suggests that persistent pain is common and often severe 1 month after surgery but is alleviated after 1 year. Clinical time course and symptoms indicate that nerve impairment rather than simple nociceptive impact may be involved in this syndrome.

Aged↗
PubMed1994

Medical aspects of the persistent vegetative state (1).

This consensus statement of the Multi-Society Task Force summarizes current knowledge of the medical aspects of the persistent vegetative state in adults and children. The vegetative state is a clinical condition of complete unawareness of the self and the environment, accompanied by sleep-wake cycles, with either complete or partial preservation of hypothalamic and brain-stem autonomic functions. In addition, patients in a vegetative state show no evidence of sustained, reproducible, purposeful, or voluntary behavioral responses to visual, auditory, tactile, or noxious stimuli; show no evidence of language comprehension or expression; have bowel and bladder incontinence; and have variably preserved cranial-nerve and spinal reflexes. We define persistent vegetative state as a vegetative state present one month after acute traumatic or nontraumatic brain injury or lasting for at least one month in patients with degenerative or metabolic disorders or developmental malformations. The clinical course and outcome of a persistent vegetative state depend on its cause. Three categories of disorder can cause such a state: acute traumatic and non-traumatic brain injuries; degenerative and metabolic brain disorders, and severe congenital malformations of the nervous system. Recovery of consciousness from a posttraumatic persistent vegetative state is unlikely after 12 months in adults and children. Recovery from a nontraumatic persistent vegetative state after three months is exceedingly rare in both adults and children. Patients with degenerative or metabolic disorders or congenital malformations who remain in a persistent vegetative state for several months are unlikely to recover consciousness. The life span of adults and children in such a state is substantially reduced. For most such patients, life expectancy ranges from 2 to 5 years; survival beyond 10 years is unusual.

Coma↗
PubMed2006

Environmental persistence of chemicals.

BACKGROUND: The hazard criterion of persistence as it applies to chemicals in the environment is reviewed and discussed. This quantity can not be measured directly in the environment, thus it must be estimated using models that synthesise information on chemical half-lives and partitioning properties, the nature of the environment and how the chemical is released into the environment. MAIN FEATURES: It is suggested that the preferred criterion is the average residence time of the chemical in the environment, i.e. conceptually the sum of the life-times of all molecules (attributable only to losses by degrading reactions) divided by the number of molecules. If all chemical fate processes are first order, this persistence is independent of the quantity of chemical introduced and whether introduction is steady- or unsteady-state in nature. It is shown that in a multimedia environment persistence is affected not only by degradation kinetics, but also by mode-of-entry and partitioning. For screening level purposes a Level II equilibrium model may be adequate but a Level III model is generally preferable for estimating the average persistence. If a distribution of persistences is required a dynamic Level IV model must be used. DISCUSSION: The implications for regulating chemicals on the basis of persistence are discussed. CONCLUSION: It is concluded that the preferred strategy is to use Level II, III, and IV models and that the use of only degradation kinetics or media-specific half-lives can be misleading and uneconomical.

Environmental Pollutants↗
PubMed1999

Value of stimulated serum thyroglobulin levels for detecting persistent or recurrent differentiated thyroid cancer in high- and low-risk patients.

BACKGROUND: Serum thyroglobulin determination has been reported to be a sensitive indicator of persistent or recurrent differentiated thyroid cancer of follicular cell origin (DTC) after total thyroidectomy. The purpose of this investigation was to determine the accuracy of serum thyroglobulin levels in predicting persistent or recurrent DTC in euthyroid and hypothyroid patients. METHODS: One hundred ninety consecutive patients with DTC of follicular cell origin who had 4 or more thyroglobulin levels measured after total thyroidectomy were retrospectively evaluated. One hundred fifteen patients had serum thyroglobulin levels measured when hypothyroid for radioiodine scanning or ablation. Serum thyroglobulin levels were determined by commercial assays. One hundred twenty-two patients less than 45 years old were considered at low risk, whereas 68 patients more than or equal to 45 years old were considered at high risk on the basis of TNM classification. The mean follow-up period was 62 months. RESULTS: After thyroidectomy with or without central or modified radical neck dissection 120 patients had normal thyroglobulin levels (< or = 3 ng/mL) while receiving thyroid hormone. One hundred thirteen of the 120 patients (94%) with normal serum thyroglobulin levels had no evidence of recurrent tumor, whereas 6% (7 patients) had persistent or recurrent disease. Among 76 patients with persistent (28 patients) or recurrent (48 patients) disease, 70 had a serum thyroglobulin level > 3 ng/mL while receiving thyroid hormone. Overall, 14 of 115 patients, including 2 of 61 (3%) in the high-risk group and 12 of 54 (22%) in the low-risk group, only had elevated serum thyroglobulin levels when hypothyroid with high serum thyroid-stimulating hormone (TSH) levels documenting persistent or recurrent disease. In 1 patient the serum thyroglobulin level (240 ng/mL) was falsely elevated probably as a result of interfering antibodies because no tumor was identified surgically or pathologically, and the thyroglobulin concentration was < 3 ng/mL when analyzed in 3 other laboratories. CONCLUSION: Serum thyroglobulin testing is sensitive (91%) and specific (99%) for identifying patients with persistent or recurrent differentiated thyroid cancer. Serum thyroglobulin levels are most precise when patients are hypothyroid (high TSH) and may be unreliable in patients with antithyroglobulin antibodies. We recommend TSH-stimulated thyroglobulin testing for all patients after total thyroidectomy for differentiated thyroid cancer of follicular cell origin regardless of patient age or risk group.

Adult↗
PubMed1992

Visible persistence is reduced by fixed-trajectory motion but not by random motion.

Despite the sluggish temporal response of the human visual system, moving objects appear clear and without blur, which suggests that visible persistence is reduced when objects move. It has been argued that spatiotemporal proximity alone can account for this modulation of visible persistence and that activation of a motion mechanism per se is not necessary. Experiments are reported which demonstrate that there is a motion-specific influence on visible persistence. Specifically, points moving in constant directions, or fixed trajectories, show less persistence than points moving with the same spatial and temporal displacements but taking random walks, randomly changing direction each frame. Subjects estimated the number of points present in the display for these two types of motion conditions. Under conditions chosen to produce 'good' apparent motion, ie small temporal and spatial increments, the apparent number of points for the fixed-trajectory condition was significantly lower than the apparent number in the random-walk condition. The traditional explanation of the suppression of persistence based on the spatiotemporal proximity of objects cannot account for these results. The enhanced suppression of persistence observed for a target moving in a consistent direction depends upon the activation of a directionally tuned motion mechanism extended over space and time.

Female↗
PubMed2004

Persistent tetrodotoxin-sensitive sodium current resulting from U-to-C RNA editing of an insect sodium channel.

The persistent tetrodotoxin (TTX)-sensitive sodium current, detected in neurons of many regions of mammalian brains, is associated with many essential neuronal activities, including boosting of excitatory synaptic inputs, acceleration of firing rates, and promotion of oscillatory neuronal activities. However, the origin and molecular basis of the persistent current have remained controversial for decades. Here, we provide direct evidence that U-to-C RNA editing of an insect sodium channel transcript generates a sodium channel with a persistent current. We detected a persistent TTX-sensitive current in a splice variant of the cockroach sodium channel gene BgNa(v) (formerly para(CSMA)). Site-directed mutagenesis experiments revealed that an F-to-S change at the C-terminal domain of this variant was responsible for the persistent current. We demonstrated that this F-to-S change was the result of a U-to-C RNA editing event, which also occurred in the Drosophila para sodium channel transcript. Our work provides direct support for the hypothesis that posttranscriptional modification of a conventional transient sodium channel produces a persistent TTX-sensitive sodium channel.

Animals↗
PubMed2005

Central role of a bacterial two-component gene regulatory system of previously unknown function in pathogen persistence in human saliva.

The molecular genetic mechanisms used by bacteria to persist in humans are poorly understood. Group A Streptococcus (GAS) causes the majority of bacterial pharyngitis cases in humans and is prone to persistently inhabit the upper respiratory tract. To gain information about how GAS survives in and infects the oropharynx, we analyzed the transcriptome of a serotype M1 strain grown in saliva. The dynamic pattern of changes in transcripts of genes [spy0874/0875, herein named sptR and sptS (sptR/S), for saliva persistence] encoding a two-component gene regulatory system of unknown function suggested that SptR/S contributed to persistence of GAS in saliva. Consistent with this idea, an isogenic nonpolar mutant strain (DeltasptR) was dramatically less able to survive in saliva compared with the parental strain. Iterative expression microarray analysis of bacteria grown in saliva revealed that transcripts of several known and putative GAS virulence factor genes were decreased significantly in the DeltasptR mutant strain. Compared with the parental strain, the isogenic mutant strain also had altered transcripts of multiple genes encoding proteins involved in complex carbohydrate acquisition and utilization pathways. Western immunoblot analysis and real-time PCR analysis of GAS in throat swabs taken from humans with pharyngitis confirmed the findings. We conclude that SptR/S optimizes persistence of GAS in human saliva, apparently by strategically influencing metabolic pathways and virulence factor production. The discovery of a genetic program that significantly increased persistence of a major human pathogen in saliva enhances understanding of how bacteria survive in the host and suggests new therapeutic strategies.

Bacteria↗
PubMed1982

Molecular comparison of delta beta-thalassemia and hereditary persistence of fetal hemoglobin DNAs: evidence of a regulatory area?

The hematological phenotypes of several Mediterranean patients with delta beta-thalassemia and hereditary persistence of fetal hemoglobin have been characterized. Although clinical and hematological characteristics are essentially superimposable in all heterozygous delta beta-thalassemics, these patients show typical G gamma/A gamma ratios in their Hb F, ranging from approximately 0.07 in Sardinian to approximately 0.15 in Sicilian and approximately 0.35 in Spanish patients. A gamma Sardinian-(isoleucine-75 leads to threonine) is found in Spanish patients and accounts for all of the A gamma production in heterozygotes, indicating that persistent production of gamma chains occurs cis to the delta beta-thalassemia gene. The molecular heterogeneity of these conditions is demonstrated by restriction enzyme mapping of DNA; Sicilian and Calabrian patients show a deletion starting from the delta-globin intron and extending several kilobases 3' to the beta-globin gene; in Spanish patients the deletion starts approximately 2-3 kilobases 5' to the delta-globin gene and extends well beyond the beta-globin gene. Comparison of these deletions with previously described ones in Negro and in a new Southern Italian case of hereditary persistence of fetal hemoglobin suggests that the deletion of a region centered at a cluster of repetitive sequences approximately 3.5 kilobases 5' to the delta-globin gene may be critical for the persistent expression of high levels of gamma-globin in hereditary persistence of fetal hemoglobin compared to delta beta-thalassemia. The concept that the deletion or mutation of specific areas (rather than nonspecific changes brought about by large deletions in the globin cluster) is important in determining the persistent expression of gamma-globin genes is supported by the finding of a nondeletion type of delta beta-thalassemia in Sardinians.

Chromosome Deletion↗
PubMed1984

Inhibition of opiate receptor-mediated signal transmission by rabies virus in persistently infected NG-108-15 mouse neuroblastoma-rat glioma hybrid cells.

Acute and persistent rabies virus infection of mouse neuroblastoma-rat glioma hybrid cells (NG-108-15) results in a loss of the normal inhibiting function of opiates via the opiate receptor on hormone-stimulated adenylate cyclase activity. Previous studies of these persistently infected cells have shown a decrease in the affinity of the opiate receptors for agonists without any change in the number of these receptors. We now demonstrate that persistently infected cells are unable to couple the opiate receptors to the inhibitory regulatory protein Ni of the adenylate cyclase, as measured by the loss of stimulation of the GTPase activity of this protein. However, the unstimulated basal GTPase activities of the regulatory components Ni and Ns are unchanged in the persistently infected cells. These studies also reveal a disorder of the stimulation of the adenylate cyclase by GTP or fluoride via the stimulating regulatory G/F protein (Ns) in persistently infected cells, whereas direct stimulation of the catalytic subunit of the adenylate cyclase by forskolin remains unchanged. Therefore, there are different points of dysfunction caused by the persistent rabies infection in the signal pathway from the opiate receptor to the adenylate cyclase and from the stimulating Ns protein to the enzyme: (i) opiate receptor binding is reduced by a decrease of agonist affinity (previously published data), (ii) the stimulation of GTPase activity of the inhibiting regulatory component Ni of the adenylate cyclase system is inhibited, and (iii) the signal pathway from the stimulating regulatory component of the adenylate cyclase system to the unchanged activity of the catalytic subunit is defective.

Adenylyl Cyclases↗
PubMed1994

Immediate early gene expression associated with the persistence of heterosynaptic long-term depression in the hippocampus.

Long-term depression (LTD) of synaptic efficacy is likely to be as important in memory processing as the more well-known long-term potentiation (LTP). The case for LTD serving as a memory mechanism, however, requires that it be shown to persist across days or weeks at least. Here we examined the persistence of heterosynaptic LTD in the medial and lateral perforant path inputs to the dentate gyrus in awake rats and correlated this persistence with the degree of immediate early gene expression as assessed immunohistochemically. Rats were chronically implanted with separate stimulating electrodes in the medial and lateral perforant paths and an extracellular field potential recording electrode in the dentate hilus. After recovery from surgery, either the medial or the lateral perforant path was tetanized with 400-Hz trains, and homosynaptic LTP and heterosynaptic LTD were followed across time. Heterosynaptic LTD was shown to occur readily in awake animals and to persist across days or weeks, depending on the stimulation protocol. The persistence of LTD and LTP was highly correlated within animals. Additional animals, given the same tetanization protocols, showed that the greatest immediate early gene expression occurred following that protocol which consistently gave the longest-lasting LTP and LTD. These data support the proposed role of LTD in memory processing but question whether immediate early genes are important for the persistence of LTP, LTD, or both.

Animals↗
PubMed2000

Induction of persistent sodium current by exogenous and endogenous nitric oxide.

Most voltage-gated Na(+) channels inactivate almost completely at depolarized membrane potentials, but in some cells a residual Na(+) current is seen that is resistant to inactivation. This persistent Na(+) current can have a profound impact on the electrical behavior of excitable cells, and the regulation of this property could have important biological consequences. However, the biological signaling mechanisms that regulate the persistence of Na(+) channels are not well understood. This study showed that in nerve terminals and ventricular myocytes nitric oxide (NO) reduced the inactivation of Na(+) current. This effect was independent of cGMP, was blocked by N-ethylmaleimide, and could be elicited in cell-free outside-out patches. Thus, a reactive nitrogen species acts directly on the channel or closely associated protein. Persistent Na(+) current could also be induced by endogenous NO generated enzymatically by NO synthase (NOS). Application of ionomycin to raise the intracellular Ca(2+) concentration in myocytes activated NOS. The NO produced in response to ionomycin was detected with an NO-sensitive fluorescent dye. Persistent Na(+) current was enhanced by the same treatment, and NOS inhibitors abolished both the elevation of NO and the induction of persistent Na(+) current. These experiments show that NO is a potential endogenous regulator of persistent Na(+) current under physiological and pathophysiological conditions.

Animals↗