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At least 163 records · Page 9Linked to original sources

PubMed2000

Empowering diabetes out-patients with structured education: short-term and long-term effects of functional insulin treatment on perceived control over diabetes.

OBJECTIVE: To investigate short-term and long-term effects of structured outpatient education for Functional Insulin Treatment (FIT: selective insulin dosages for eating, fasting or correcting hyperglycaemia) on perceived control over diabetes and related health beliefs. FIT was thought to influence the perception of self-efficacy in diabetes, in contrast to conventional treatment, based on scheduled, rigid food intake and insulin delivery--it allows flexible eating, provided independent control of glycemia. METHODS: Structured, comprehensive, outpatient group training in FIT for selective use of insulin either for eating, fasting or correction included practical "insulin games." The FIT program focused on everyday criteria for choices of insulin dosages and thus on the patient's ability to execute his/her newly gained flexible treatment to his/her everyday life while preventing acute and late complications. To evaluate effects of FIT on "Perceived Control over Diabetes" and related "Health Beliefs Concerning Diabetes" (Bradley's questionnaires, 1984), a fully randomized short-term controlled Study 1 (four weeks, 32 patients), and long-term uncontrolled pilot Study 2 (three years, 68 patients) were performed. RESULTS: The short-term study revealed that FIT induced the feeling of independence from situational control while self-managing diabetes. In the long-term study, the patients were increasingly freed from the feeling of being under the control of physician and treatment-related restrictions, which--together with higher perceived self-efficacy--contributed to the feeling of "empowerment." This was associated with high treatment satisfaction and significant improvement of glycemic control. CONCLUSION: Structured out-patient group training for FIT results in measurable improvement of patients' perceived control over diabetes and self-efficacy.

Adolescent↗

PubMed1986

[Increased activity of sympatho-adrenomedullary system and decreased renal dopamine receptor content after short-term and long-term sodium loading in rats].

UNLABELLED: We investigated the effects of short-term and long-term sodium loading on the sympathoadrenomedullary system and renal dopamine receptor. Male Wistar rats (n = 30) were raised drinking 1% NaCl for four weeks. Urinary norepinephrine and epinephrine excretion (UNE and UE) were measured before and 1, 2, 4 weeks after sodium loading by the use of high pressure liquid chromatography with fluorescence spectrophotometer. Renal plasma membranes were prepared by the ultracentrifugation method, and maximal binding capacity (Bmax) and dissociation constant (Kd) of renal dopamine receptor were determined by Scatchard analysis using 3-H-spiperone. RESULTS: Sodium loading caused a slight but not significant decrease of free UNE after 1 and 2 weeks then clear increments of total (free + conjugated) UNE, free UE and total UE after 4 weeks. Bmax of renal dopamine receptor did not change after 1 and 2 weeks but significantly decreased after 4 weeks (before: 535.9 fmol/mg X protein, after 4 weeks: 327.2 fmol/mg X protein). Kd of renal dopamine receptor slightly elevated 1 week after sodium loading and then returned to the initial level. CONCLUSION: These data suggest that short-term sodium loading may suppress the sympathetic activity, but long-term sodium loading may increase the activity of the sympathoadrenomedullary system with the decrease of renal dopamine receptor concentration. Increased catecholamines and decreased renal dopamine after long-term sodium loading may contribute to sodium-dependent hypertension.

Adrenal Medulla↗

PubMed2005

The effects of short-term and long-term pulmonary rehabilitation on functional capacity, perceived dyspnea, and quality of life.

STUDY OBJECTIVES: The purposes of this study were as follows: (1) to determine whether physical performance, quality of life, and dyspnea with activities of daily living improved following both short-term and long-term pulmonary rehabilitation (PR) across multiple hospital outpatient programs; (2) to examine the differences in these parameters between men and women; and (3) to determine what relationships existed between the psychosocial parameters and the results of the 6-min walk (6MW) test performance across programs. DESIGN: Non-experimental, prospective, and comparative. SETTING: Seven outpatient hospital PR programs from urban and rural settings across North Carolina. PARTICIPANTS: Three hundred nine women and 281 men who were 20 to 93 years of age (mean [+/- SD] age, 66.7 +/- 11.1 years) with chronic lung disease. INTERVENTIONS: All 6MW tests and health surveys were administered prior to and immediately following 12 and 24 weeks of supervised PR participation. Scores from the 6MW tests, the Ferrans and Powers quality of life index-pulmonary version III (QLI), the Medical Outcomes Study 36-item short form (SF-36), and the University of California at San Diego shortness of breath questionnaire (SOBQ) were compared at PR entry, at 12 weeks, and at 24 weeks for differences by gender with repeated-measures analysis of variance. The study entry and follow-up SF-36 physical and mental component summary scores, the QLI health/function and overall scores, and the SOBQ scores were also compared to the 6MW test scores with Pearson correlation coefficient analysis. RESULTS: The mean summary scores on the SF-36 and the QLI increased after 12 weeks of PR (p < 0.05), and improvements were maintained by 24 weeks of PR participation (p < 0.05). Scores on the SOBQ improved after 12 weeks (p < 0.001) among the short-term participants, but not until after 24 weeks among the long-term participants (p = 0.009). The 6MW test performance improved after 12 weeks (p < 0.001) and again from 12 to 24 weeks (p = 0.002) in the long-term participants. No relevant correlational relationships were found between 6MW scores and the summary scores of the administered surveys (r = -0.43 to 0.36). CONCLUSIONS: Physical performance, as measured by the 6MW test, continued to improve with up to 24 weeks of PR participation. Quality-of-life measures and the perception of dyspnea improved after 12 weeks of PR participation, with improvements maintained by 24 weeks of PR participation. It is recommended that PR patients participate in supervised PR for at least 24 weeks to gain and maintain optimal health benefits.

Activities of Daily Living↗

PubMed1995

Short-term and long-term effects of p-chloroamphetamine on hippocampal serotonin and corticosteroid receptor levels.

Hippocampal corticosteroid receptors are regulated by corticosterone as well as by neurotransmitters, such as serotonin (5-HT). Studies have demonstrated that long-term changes in 5-HT levels are associated with alterations in hippocampal glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) number. However, the effect of short-term manipulations of 5-HT levels on hippocampal corticosteroid receptor levels has not been thoroughly investigated. The present set of studies examined the effect of para-chloroamphetamine (PCA) administration on both short-term and long-term regulation of hippocampal 5-HT and corticosteroid receptor levels. PCA is a selective serotonergic neurotoxin which initially releases 5-HT to cause a short-term depletion of 5-HT stores, followed by a long-term decrease in 5-HT levels which presumably reflects the destruction of 5-HT nerve terminals. In the initial study rats were adrenalectomized and 24 h later injected with PCA (20 mg/kg) and sacrificed 3 h later. PCA produced a large decrease in hippocampal 5-HT (-79%) and 5-hydroxyindoleacetic acid (5-HIAA) (-40%) concentrations. In addition, PCA significantly decreased both hippocampal GR (-28%) and MR (-35%) levels. Pretreatment with fluoxetine (20 mg/kg), which presumably blocks the uptake of PCA into 5-HT nerve terminals, completely blocked the PCA-induced decreases in both 5-HT and corticosteroid receptor concentrations. In a final experiment, the long-term (7 days) effect of PCA administration on hippocampal 5-HT and corticosteroid receptor levels was examined. PCA (10 mg/kg given on 2 consecutive days) was administered to adrenal-intact rats which were adrenalectomized 6 days later and subsequently sacrificed following a 24 h interval. PCA produced an 87% decrease in hippocampal 5-HT and 5-HIAA levels, but did not alter hippocampal GR or MR levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

PubMed2001

Nicotine accelerates reversal of long-term potentiation and enhances long-term depression in the rat hippocampal CA1 region.

In the hippocampal CA1 region, low-frequency stimulation (LFS; 200 pulses at 1 Hz) causes reversal of long-term potentiation (depotentiation, DP) and long-term depression (LTD), both of which are thought to be the cellular substrate of learning and memory. Because nicotine enhances learning and memory, we examined if nicotine modulates DP and LTD in the hippocampal CA1 region. Bath application of nicotine during LFS accelerated DP, that is, potentiated synaptic responses in hippocampal CA1 neurons returned to pre-tetanic control levels more rapidly in the presence of nicotine. Because a similar acceleration of DP was observed using the alpha7 nicotinic acetylcholine receptor (nAChR)-selective antagonist methyllcaconitine (MLA), the nicotine effect appeared to be at least partly mediated by nicotine-induced desensitization of alpha7 nAChRs. Delivery of LFS in the presence of nicotine or MLA also depressed synaptic responses in a naive pathway and facilitated LTD, that is, the magnitude of LTD was larger when the drug was present during LFS. Thus, these results demonstrate that nicotine facilitates DP and LTD, which may represent, at least in part, the cellular mechanism underlying nicotine-induced cognitive enhancement.

Aconitine↗

PubMed1998

Short-term and long-term inhibition of endogenous atrial natriuretic peptide in dogs with early-stage heart failure.

Early-stage heart failure (HF) is characterized by an increase in circulating atrial natriuretic peptide (ANP) without activation of the renin-angiotensin-aldosterone system (RAAS) or body fluid retention. To test the hypothesis that elevated endogenous ANP suppresses the RAAS, maintains body fluid balance, and regulates vascular tone in early-stage HF, we assessed the effects of short-term and long-term inhibition of ANP on cardiorenal and neurohormonal functions. Short-term antagonism was produced by bolus administration (3 mg/kg) of HS-142-1, an antagonist of guanylate-cyclase coupled ANP receptors, and long-term antagonism was produced by continuous infusion (1 mg/kg per h) of HS-142-1 for 8 h to dogs with early-stage HF induced by rapid ventricular pacing (270 beats/min, 8 days). In this experimentally produced HF, plasma ANP was significantly increased relative to the pre-pacing value, but not plasma renin activity (PRA) or plasma aldosterone level. HS-142-1 significantly suppressed plasma and urinary guanosine 3',5'-cyclic monophosphate (cGMP) levels, markers of endogenous ANP activity, in both experiments. Although mean arterial pressure and cardiac output did not change significantly, pulmonary capillary wedge pressure and right atrial pressure were elevated in both experiments. While short-term inhibition of ANP did not change PRA and aldosterone levels, long-term inhibition significantly increased these hormonal levels, resulting in decreases in urine flow rate, urinary sodium excretion rate, glomerular filtration rate, and renal plasma flow. These findings suggest that endogenous ANP plays a critical role in regulating venovascular tone, inhibiting activation of RAAS, and maintaining renal functions in early-stage HF.

Animals↗

PubMed1995

Endoscopic treatment of postoperative colonic strictures using an achalasia dilator: short-term and long-term results.

BACKGROUND AND STUDY AIMS: Endoscopic dilation has proven to be a valid therapeutic alternative to surgery for treating postoperative anastomotic colonic strictures. The authors here evaluate retrospectively the short and long-term clinical results obtained in such patients by pneumatic dilation. PATIENTS AND METHODS: From March 1986 to December 1993, 18 patients who had undergone surgery for colorectal cancer were treated for a postoperative symptomatic stricture. Four patients had undergone a left hemicolectomy and 14 an anterior resection. The strictures had a diameter of less than 2 mm, and a length ranging from 5 to 29 mm. The dilations were performed using a 30-40 mm pneumatic dilator for achalasia. The clinical results were classified in relation to the abdominal symptomatology reported by the patients, and were evaluated in the short term (one week) and long term (mean follow-up: 39 months). RESULTS: Seventeen of the 18 patients underwent a total of 45 dilating sessions; one patient was excluded because a recurrence was diagnosed at the suture line. Five patients had a single dilating session; eight patients had two sessions, and four patients had a mean of 4.5 sessions. Two complications were observed: a punctiform bowel perforation and one transient mucosal bleeding. Immediate symptomatic relief was achieved in all cases, and good long-term clinical results were achieved in 16 patients (94.1%). CONCLUSIONS: Endoscopic dilation with an achalasia balloon has proved to be safe and simple to perform, and allowed us to obtain good short-term and long-term clinical results. This type of dilation may be considered the first-line therapeutic approach for symptomatic benign colonic anastomotic strictures.

Adult↗

PubMed2003

p38 MAP kinase mediates both short-term and long-term synaptic depression in aplysia.

At Aplysia sensory-to-motor neuron synapses, the inhibitory neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFa) produces depression, and serotonin (5-HT) produces facilitation. Short-term depression has been found to result from the activation of a phospholipase A2. The released arachidonate is metabolized by 12-lipoxygenase to active second messengers. We find that FMRFa leads to the phosphorylation and activation of p38 mitogen-activated protein (MAP) kinase. Short-term depression and the release of arachidonate are blocked by the specific p38 kinase inhibitor SB 203580. Both the inhibitor and an affinity-purified antibody raised against recombinant Aplysia p38 kinase injected into sensory neurons prevented long-term depression, which depends on the phosphorylation of translation factors cAMP response element-binding protein 2 (CREB2) and activating transcription factor 2. Facilitation produced by 5-HT, on the other hand, inactivates p38 kinase. Chromatin immunoprecipitation assays indicate that p38 kinase activates CREB2. p38 kinase also is pivotal in the bidirectional regulation of synaptic plasticity: when the kinase is inhibited, brief treatment with 5-HT that normally produces only short-term facilitation now results in long-term facilitation. Conversely, in sensory neurons injected with the activated kinase, long-term facilitation is blocked, and brief exposure to FMRFa, which normally results in short-term depression, results in long-term depression. We conclude that p38 kinase, which itself is bidirectionally regulated by FMRFa and 5-HT, acts as a modulator of synaptic plasticity by positively regulating depression and serving as an inhibitory constraint for facilitation.

Activating Transcription Factor 2↗

PubMed1991

Short-term and long-term memory in single cells.

Many approaches have been used to study short- and long-term memory. Bacteria detect chemical gradients using a memory obtained by the combination of a fast excitation process and a slow adaptation process. This model system, which has the advantages of extensive genetic and biochemical information, shows no features of long-term memory. To study long-term memory, neural cell line systems have been developed that exhibit two phenomena associated with learning and memory, habituation and potentiation. The expression of these phenomena in clonal cell lines, devoid of synaptic connections, makes it possible to study the biochemical and molecular mechanisms that contribute to short-term and long-term memory.

Acetylcholine↗

PubMed1996

Zidovudine phosphorylation after short-term and long-term therapy with zidovudine in patients infected with the human immunodeficiency virus.

BACKGROUND: Resistance of human immunodeficiency virus (HIV) to zidovudine (AZT) has been associated with mutations in the viral reverse transcriptase gene. However, recent studies suggest that host cellular factors such as a decreased thymidine kinase activity or an increased cellular P-glycoprotein expression may be important. This study compared concentrations of zidovudine monophosphate, zidovudine diphosphate, and zidovudine triphosphate with P-glycoprotein expression in peripheral blood mononuclear cells from patients receiving long-term (> 18 months) and short-term (< 2 months) zidovudine treatment. METHODS: Ten subjects in the short-term group and 11 subjects in the long-term group with CD4 counts between 300 and 500 received a single oral dose of zidovudine (200 mg) after a 24-hour washout period. Blood samples were collected at 0, 1, 2, 4, and 6 hours. Intracellular nucleotide concentrations were measured by a combined HPLC-radioimmunoassay method, and P-glycoprotein expression was determined by fluorescence activated cell sorting (FACS) analysis with use of the monoclonal mouse antibody MRK-16. RESULTS: Zidovudine monophosphate was the predominant compound, accounting for 73.4% +/- 7.1% (SD) of the total phosphates in the long-term treatment group and 74.2% +/- 15.0% (SD) in the short-term group. Zidovudine diphosphate accounted for 13.3% +/- 3.3% (SD) in the long-term group and 12.5% +/- 6.6% (SD) in the short-term group. Zidovudine triphosphate accounted for 13.4% +/- 4.1% (SD) in the long-term group and 13.5% +/- 8.3% (SD) in the short-term group. Mean peak concentrations for the active zidovudine triphosphate were 0.04 +/- 0.02 (SD) pmol/10(6) cells in both groups. Comparison of the individual zidovudine phosphate concentrations and P-glycoprotein expression revealed no significant difference in the two patient populations. CONCLUSIONS: These data suggest that intracellular phosphorylation does not change over time and that zidovudine does not select for P-glycoprotein expressing cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Relationship between short- and long-term memory and short- and long-term extinction.

Both the acquisition and the extinction of memories leave short- and long-term mnemonic traces. Here, we show that in male Wistar rats, the short-term memory for a step-down inhibitory avoidance task (IA) is resistant to extinction, and that its expression does not influence retrieval or extinction of long-term memory. It has been known for some time that short- and long-term inhibitory avoidance memory involve separate and parallel processes. Here we show that, instead, short-term extinction of IA long-term memory is the first step towards its long-term extinction, and that this link requires functional NMDA receptors and protein synthesis in the CA1 region of the dorsal hippocampus at the time of the first CS-no US presentation.

Animals↗

PubMed2001

St John's wort, hypericin, and imipramine: a comparative analysis of mRNA levels in brain areas involved in HPA axis control following short-term and long-term administration in normal and stressed rats.

Clinical studies demonstrate that the antidepressant efficacy of St John's wort (Hypericum) is comparable to that of tricyclic antidepressants such as imipramine. Onset of efficacy of these drugs occurs after several weeks of treatment. Therefore, we used in situhybridization histochemistry to examine in rats the effects of short-term (2 weeks) and long-term (8 weeks) administration of imipramine, Hypericum extract, and hypericin (an active constituent of St John's wort) on the expression of genes that may be involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Imipramine (15 mg kg(-1)), Hypericum (500 mg kg(-1)), and hypericin (0.2 mg kg(-1)) given daily by gavage for 8 weeks but not for 2 weeks significantly decreased levels of corticotropin-releasing hormone (CRH) mRNA by 16-22% in the hypothalamic paraventricular nucleus (PVN) and serotonin 5-HT(1A) receptor mRNA by 11-17% in the hippocampus. Only imipramine decreased tyrosine hydroxylase (TH) mRNA levels in the locus coeruleus (by 23%), and only at 8 weeks. The similar delayed effects of the three compounds on gene transcription suggests a shared action on the centers that control HPA axis activity. A second study was performed to assess the effects of long-term imipramine and Hypericum administration on stress-induced changes in gene transcription in stress-responsive circuits. Repeated immobilization stress (2 h daily for 7 days) increased mRNA levels of CRH in the PVN, proopiomelanocortin (POMC) in the anterior pituitary, glutamic acid decarboxylase (GAD 65/67) in the bed nucleus of the stria terminalis (BST), cyclic AMP response element binding protein (CREB) in the hippocampus, and TH in the locus coeruleus. It decreased mRNA levels of 5-HT(1A) and brain-derived neurotrophic factor (BDNF) in the hippocampus. Long-term pre-treatment with either imipramine or Hypericum reduced to control levels the stress-induced increases in gene transcription of GAD in the BST, CREB in the hippocampus, and POMC in the pituitary. The stress-induced increases in mRNA levels of CRH in the PVN and TH in the locus coeruleus were reduced by imipramine but not by Hypericum. The stress-induced decreases in BDNF and 5-HT(1A)mRNA levels were not prevented by either drug. Taken together, these data show: (1) that Hypericum and hypericin have delayed effects on HPA axis control centers similar to those of imipramine; and (2) that select stress-induced changes in gene transcription in particular brain areas can be prevented by long-term treatment with either the prototypic tricyclic antidepressant imipramine or the herbiceutical St John's wort. However, imipramine appears to be more effective in blocking stress effects on the HPA axis than the plant extract.

Adrenal Glands↗

PubMedDate not supplied

Short-term and long-term UVB-induced immunosuppression in human skin exhibit different ultrastructural features.

Short-term ultraviolet B light (UVB)-induced immune suppression was established by the ability of UVB to inhibit induction of allergic contact dermatitis (ACD) to dinitrochlorobenzene (DNCB). The long-term effect was assessed by a dramatic reduction of the mixed-epidermal cell lymphocyte reaction (MECLR) responses. Immuno electron microscopic (IEM) investigation of HLA class II localization on epidermal Langerhans cells (LC) (pivotal for the immune response of the skin) showed no difference in HLA class II expression after UVB-exposure compared to control skin, both after short-term and long-term UVB-exposure. Ultrastructural examination of the epidermis revealed a normal appearance of the epidermal cells after long-term UVB-exposure. However, after short-term UVB-exposure the epidermis exhibited many abnormalities, ranging from the stratum corneum to the basal membrane. So although both short- and long-term UVB exposures were able to cause immune suppression in the skin, those processes were not accompanied with identical morphological epidermal features.

Dermatitis, Allergic Contact↗

PubMed1997

Nitric oxide facilitates long-term potentiation, but not long-term depression.

Reports that nitric oxide synthase (NOS) inhibition prevents the induction of long-term potentiation (LTP) have been controversial. Recent evidence suggests that NO may help to regulate the threshold for LTP induction. We have tested this hypothesis by examining the effects of stimulus frequency and train duration on synaptic plasticity in the presence of either NO donors or NOS inhibitors. Two different NO donors facilitated LTP induction by stimuli that normally produced only short-term potentiation, whereas NOS inhibitors blocked LTP to stimuli that normally produce small LTP. NO donors facilitated LTP induction even when NMDA receptors were blocked, indicating that NO need not act via NMDA receptors. NO donors and NOS inhibitors were without effect on long-term depression (LTD), suggesting that they act on a distinct potentiating mechanism. Thus, NO could contribute to the establishment of plasticity under physiologically relevant conditions by selectively increasing the probability of LTP induction.

2-Amino-5-phosphonovalerate↗

PubMed2005

The metabotropic glutamate receptor mGluR3 is critically required for hippocampal long-term depression and modulates long-term potentiation in the dentate gyrus of freely moving rats.

Group II metabotropic glutamate receptors (mGluRs) play an important role in the regulation of hippocampal synaptic plasticity in vivo: long-term potentiation (LTP) is inhibited and long-term depression (LTD) is enhanced by activation of these receptors. The contribution, in vivo, of the individual group II mGluR subtypes has not been characterized. We analysed the involvement of the subtype mGluR3 in LTD and LTP. Rats were implanted with electrodes to enable chronic measurement of evoked potentials from medial perforant path-dentate gyrus synapses. Neither the selective mGluR3 agonist, N-acetylaspartylglutamate (NAAG), nor the antagonist beta-NAAG, given intracerebrally, affected basal synaptic transmission. beta-NAAG significantly inhibited LTD expression. NAAG exhibited transient inhibitory effects on the intermediate phase of LTD. Whereas NAAG altered paired-pulse responses, beta-NAAG had no effect, suggesting that antagonism of mGluR3 prevents LTD via a postsynaptic mechanism, whereas agonist activation of mGluR3 modulates LTD at a presynaptic locus. NAAG impaired the expression of LTP, whereas beta-NAAG had no effect. NAAG effects on LTP were blocked by EGLU, a selective group II mGluR antagonist. Our data suggest an essential role for mGluR3 in LTD, and a modulatory role for mGluR3 in LTP, with effects being mediated by distinct pre- and post-synaptic loci.

Animals↗

PubMed2006

A tropomyosin-related kinase B ligand is required for ERK activation, long-term synaptic facilitation, and long-term memory in aplysia.

BDNF, which acts through tropomyosin-related kinase B (TrkB) receptors during mammalian development, also enhances long-term synaptic facilitation (LTF) in adult Aplysia. Because LTF is a substrate for long-term memory (LTM) in Aplysia, we examined the requirement of a secreted TrkB ligand in LTM formation at molecular, synaptic, and behavioral levels. Using an extracellular fusion protein that sequesters secreted TrkB ligands, we show that TrkB function is required for serotonin-induced activation of extracellular signal-regulated kinase, tail nerve shock-induced LTF in the CNS, and tail shock-induced LTM but is not necessary for short-term synaptic facilitation or short-term memory. These results show that a secreted growth factor, acting through a TrkB signaling cascade, is critical for the induction of long-lasting plasticity and memory formation in Aplysia.

Animals↗

PubMed2002

Soluble oligomers of beta amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus.

The dementia in Alzheimer disease (AD) is usually attributed to widespread neuronal loss in conjunction with the pathologic hallmarks of intracellular neurofibrillary tangles and extracellular plaques containing amyloid (A beta) in fibrillar form. Recently it has been demonstrated that non-fibrillar assemblies of A beta possess electrophysiologic activity, with the corollary that they may produce dementia by disrupting neuronal signaling prior to cell death. We therefore examined the effects of soluble oligomers of A beta(1-42) on long-term potentiation (LTP) and long-term depression (LTD), two cellular models of memory, in the dentate gyrus of rat hippocampal slices. Compared with vehicle controls, slices pre-incubated 60 min in the presence of A beta-derived diffusible ligands (ADDLs) showed no differences in threshold intensity to evoke a synaptic response, slope of field excitatory post-synaptic potentials (EPSPs), or the input/output function. Tetanus-induced LTP and reversal of LTD were strongly inhibited in ADDLs-treated slices whereas LTD was unaffected. These data suggest that soluble non-fibrillar amyloid may contribute to the pathogenesis of AD both by impairing LTP/memory formation at the cellular level and by creating 'neuroplasticity imbalance' manifested by unopposed LTD in the setting of impaired capacity for neural repair via reversal of LTD or LTP.

Amyloid beta-Peptides↗

PubMed1998

[Short-term versus long-term use of nitrates in acute myocardial infarction].

While previous experimental and small-scaled clinical studies have shown intravenous administration of nitroglycerin in the setting of acute myocardial infarction reduced infarct size and diminished the frequency of mechanical complications, its effect on short-term and long-term outcome has not been established. Recently, two large-scaled clinical trials, GISSI-3 and ISIS-4, have demonstrated unexpected neutral effect of nitrates on subacute phase mortality after myocardial infarction. Long-term nitrate treatment, however, has been indicated by three independent clinical studies that it may increase cardiac events in patients with healed myocardial infarction. Although a large-scaled randomized clinical trial is required to confirm the deleterious effect of nitrates on long-term outcome after myocardial infarction, routine use of nitrates in chronic phase of coronary heart disease cannot be recommended.

Clinical Trials as Topic↗