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Significance of ST-segment and T wave changes in the resting electrocardiograms of patients with exertional angina, studied by exercise radionuclide angiocardiograms.

In order to investigate the clinical significance of ST-T changes in resting ECG in angina pectoris, symptom-limited ergometer exercise radionuclide angiocardiography with ECG was performed in 60 patients with exertional angina. In those with normal ECG at rest (Group N), left ventricular ejection fraction (EF) did not change during exercise (71 +/- 5% to 71 +/- 6%). In those with only ST change at rest (Group ST) and those with only T change at rest (Group T), EF decreased significantly during exercise (68 +/- 5% to 63 +/- 7%, p less than 0.01; 68 +/- 6% to 61 +/- 7%, p less than 0.001). In those with ST and T changes at rest (Group ST + T), EF was low at rest (58 +/- 11%) and decreased further at exercise (52 +/- 8%, p less than 0.001). In those whose negative or flat T wave became more negative during exercise, EF was low both at rest and at exercise. In conclusion, ST and T changes at rest in patients with exertional angina might suggest a depressed reserve of myocardial function for exercise.

Adult↗

The effect of prolonged rest on calcium exchange and contractions in rat and guinea-pig ventricular myocardium.

The exchange of calcium in isolated, perfused rat ventricular myocardium was measured by means of 45Ca2+ and compared with that in guinea-pig. In the rat the total exchangeable calcium pool containing 0.84 +/- 0.03 mmol/kg of wet weight (w.w.) consists of at least two fractions: excitation-dependent, beat-to-beat exchanging fraction of about 0.1 mmol/kg w.w. which is lost at rest and re-gained during post-rest contractions; a fraction containing 0.74 +/- 0.04 mmol/kg w.w. of Ca2+ exchanging both at rest and during stimulation. During prolonged rest the rat ventricular myocardium loses only 13% (0.1 mmol/kg w.w.) of its exchangeable calcium whereas in the ventricle of guinea-pig heart 72% (0.94 mmol/kg w.w.) Ca2+ is lost at rest. These differences conform to the differences in the response of the contractile force to prolonged rest: the first post-rest contraction of the rat ventricle is stronger than the steady-state beats whereas the guinea-pig ventricular muscle loses its contractility. These results are compatible with the hypothesis that the calcium fraction released from resting guinea-pig ventricle is an important component of the mechanism of the slow force-frequency relationship.

Animals↗

The effect of occlusal rest size and shape on yield strength.

STATEMENT OF PROBLEM: Occlusal rests, essential for conventional removable partial dentures, may fracture and cause failure of the prosthesis. It is unknown whether alterations in the size or shape of occlusal rests might improve their performance. PURPOSE: In this in vitro study, 3-dimensional finite element analysis was used to evaluate the effects of occlusal rest size and shape on yield strength. MATERIAL AND METHODS: An occlusal rest and a minor connector as part of a clasp assembly were modeled for 3-dimensional finite element analysis with 3 variations of width (2.0, 3.0, and 4.0 mm), thickness (0.7, 1.0, and 1.5 mm) and length (2.0, 3.0, and 4.0 mm). A concentrated vertical load of 100 N was applied at the most protruded point of the occlusal rest base. Maximal principal stress and yield strength were calculated. In addition, the following parameters were altered: radius of curvature at the inner connection (r), thickness of the minor connector (m), inclination of horizontal axis of occlusal rest (i), and thickness at the most protruded point (t). RESULTS: Yield strength increased with increased width (183% to 242% from 2.0 to 4.0 mm) and thickness (141% to 230% from 0.7 to 1.5 mm). Alterations in length had a lesser effect on yield strength (120% to 178% from 4.0 to 2.0 mm). All other parameters except thickness at the most protruded point (t) affected yield strength. CONCLUSION: The results of this in vitro study suggest basic principles for optimizing the size and shape of occlusal rests. In general, increased width and thickness are desirable, whereas overrounded or sharp line angles and excessive rest inclination should be avoided. These principles may be useful in removable partial denture design.

Computer Simulation↗

Evidence of reduced resting blood flow in viable myocardial regions with chronic asynergy.

OBJECTIVES: We tested the hypothesis in patients (n = 24) with ischemic heart disease that chronic contractile dysfunction occurs in myocardial regions with true reduction in rest blood flow. BACKGROUND: Whether viable myocardial regions with chronic contractile dysfunction have true reduction in rest myocardial blood flow is controversial. METHODS: Positron emission tomography (PET) 13N-ammonia was used to measure myocardial blood flow in combination with 18F-fluorodeoxyglucose (18FDG) to assess myocardial viability. Viability also was assessed by dobutamine echo and recovery of function after coronary artery bypass grafting (CABG). Segments (n = 252) were selected based on PET measured reduced resting blood flow and rest asynergy on echo. RESULTS: Regional myocardial viability was present in 20 of 23 patients by PET, 13 of 23 by dobutamine echo and 10 of 11 by postrevascularization criteria. Rest blood flow in normal regions was 1.14+/-0.52 ml/min/g and by definition exceeded (p < 0.005) that in both viable (0.48+/-0.15; n = 8 patients) and nonviable (0.45+/-0.14; n = 8 patients) regions (post-CABG criteria), which did not differ. Correction of rest myocardial blood flow in viable asynergic segments, only, for fibrosis and incomplete tracer recovery raised the level to 0.67+/-0.21 (p < 0.005 vs. normal). Finally, evidence of both stunning (rest asynergy with normal flow) and hibernation was present in 15 of 23 (65%) patients. CONCLUSIONS: Reduced rest blood flow in viable myocardial regions with chronic asynergy is common and cannot be accounted for by partial volume effect. Thus, hypotheses concerning physiologic mechanisms underlying chronic contractile dysfunction should consider the role played by chronic reduction of basal myocardial blood flow.

Adult↗

Quantitative comparison of single-isotope and dual-isotope stress-rest single-photon emission computed tomographic imaging for reversibility of defects.

BACKGROUND: Dual-isotope rest/stress single-photon emission computed tomographic (SPECT) imaging is a time-saving imaging protocol. However, the stress radiotracer, technetium 99m-labeled sestamibi, and the rest radiotracer, thallium 201, have different physical properties and myocardial kinetics. In patients with abnormal resting myocardial perfusion, these differences may affect quantification of rest defect size and defect reversibility. The purpose of the study was to compare myocardial perfusion defect reversibility quantitatively by single-isotope (rest/stress sestamibi) and dual-isotope (rest thallium/stress sestamibi) SPECT. METHODS AND RESULTS: Thirty patients with prior myocardial infarction underwent rest/stress sestamibi SPECT imaging and rest thallium SPECT imaging. Defects were quantified according to circumferential count profiles with a normal sestamibi database. The images of a subgroup of 21 patients were processed with radiotracer-specific normal databases. Defect size and defect reversibility were compared quantitatively for single-isotope and dual-isotope SPECT. Rest sestamibi defect size was significantly larger than rest thallium defect size (19 +/- 15 vs 14 +/- 16; p = 0.007). Defect reversibility was larger with thallium than with sestamibi (10 +/- 9 vs 6 +/- 6; p = 0.002). With radiotracer-specific normal databases, mean rest sestamibi and thallium defect sizes in 21 patients were not different (23 +/- 19 vs 21 +/- 17; difference not significant). With radiotracer-specific normal databases, mean defect reversibility was not different with either sestamibi or thallium (6 +/- 6 vs 8 +/- 9; difference not significant), although correlation among individual patients was only fair (r2 = 0.48). CONCLUSION: In patients with prior myocardial infarction, stress-induced defect reversibility is quantitatively larger with dual-isotope imaging than with single-isotope imaging. Quantitative processing of dual-isotope images requires radiotracer-specific normal databases. Because of different characteristics of sestamibi and thallium, assessment of defect reversibility on dual-isotope images should be made with caution. Only relatively large defect reversibility can be assumed to represent true stress-induced myocardial ischemia.

Dipyridamole↗

Altered biochemical markers of bone turnover in humans during 120 days of bed rest.

Microgravity induces significant and progressive bone loss in both humans and animals. This is the consequence of disturbed bone remodeling. We performed a bed rest experiment to simulate microgravity and tried to clarify bone metabolism by measuring biochemical markers of bone turnover. Six healthy volunteers participated in 120 days of bed rest. The parameters of calcium homeostasis, calcitropic hormones, and biochemical markers of bone turnover were examined. After ambulatory control evaluation, all subjects underwent 120 days of bed rest. Metabolic evaluation was performed in a baseline period, and on days 7, 16, 50, 72, 92, and 108 during bed rest, and on days 10 and 25 during a recovery period. Bed rest induced an increase in urinary calcium (Ca) excretion and serum Ca and bone resorption markers. Urine pyridinoline, deoxypyridinoline, and type I collagen cross-linked N-telopeptide increased more rapidly than urinary Ca excretion and serum Ca. Tartrate-resistant acid phosphatase (TRAP) increased even in the recovery period. Carboxy-terminal propeptide of type I collagen, a bone formation marker, significantly decreased on days 50, 92, and 108 of bed rest. These changes of biochemical markers of bone metabolism, except for TRAP, rapidly returned toward control levels in the recovery period. Immunoreactive parathyroid hormone showed a modest decrease during bed rest and a significant increase in the recovery period. Insulin-like growth factor I (IGF-I) and its binding protein, insulin-like growth factor binding protein-3, increased during bed rest, indicating the possibility of resistance to IGF-I in bones under reduced mechanical stress and strain. Bone loss from unloading results from the combination of acceleration of bone resorption and subsequent retardation of bone formation.

Adult↗

Maternal control of resting-egg production in Daphnia.

Many planktonic organisms produce 'resting' stages when the environmental conditions deteriorate. Like seeds, resting stages can survive unfavourable conditions. The crustacean Daphnia normally reproduces by means of parthenogenetically produced normal, not resting, eggs-but occasionally switches to bisexual reproduction, which results in two resting eggs encased in a robust structure carried on the back of the female. This 'ephippium' is shed with the next moult, and can survive dormant for many years. The induction of resting-egg production requires multiple environmental stimuli, one of them being photoperiod. The switch from production of parthenogenetic eggs to resting eggs in Daphnia has recently been shown to be influenced by a maternal food effect. Here we present evidence that female Daphnia transmit information not only about food but also on photoperiod to their offspring, and influence the production of resting eggs in the next generation. The combined maternal effects can be relevant for the correct timing of resting-egg production-for example, in discriminating between spring and autumn conditions.

Animals↗

Increased Ca2+ influx in the resting state maintains the myogenic tone and activates charybdotoxin-sensitive K+ channels in dog basilar artery.

We examined whether Ca2+ channel function in the resting state alters the resting tone and Ca(2+)-activated K+ (KCa) channel function in dog basilar artery: data were compared with findings in the mesenteric artery. Isolated dog basilar artery maintained a myogenic tone; that is, the resting tone decreased when either the Krebs solution was replaced with a Ca(2+)-free solution or nifedipine was added. The basal 45Ca influx in the resting state of the basilar artery was significantly increased compared with that in the mesenteric artery, and this increase in the basilar artery was reduced by nifedipine. The addition of charybdotoxin (ChTX), a blocker of large-conductance KCa channels, to the resting strips caused a concentration-dependent contraction in the basilar artery but not in the mesenteric artery. The ChTX-induced contraction in the basilar artery was abolished by nifedipine. In resting strips preloaded with 86Rb, the basal 86Rb efflux rate constant was significantly greater in the basilar artery than in the mesenteric artery. The addition of nifedipine to the resting strips decreased the basal 86Rb efflux rate constant only in the basilar artery. These results suggest that the transmembrane Ca2+ influx via L-type voltage-dependent Ca2+ channels was significantly increased in the resting state of the basilar artery and that the myogenic tone was therefore maintained and the ChTX-sensitive KCa channels were highly activated.

Animals↗

Transcriptional repression by the zinc finger protein REST is mediated by titratable nuclear factors.

The zinc finger protein REST (RE-1 silencing transcription factor) is a transcriptional repressor that inhibits neuronal gene transcription in non-neuronal tissues. REST may represent a master regulator of neuronal gene expression. REST contains two repressor domains located at the N- and C-termini of the molecule. To investigate the molecular mechanism of transcriptional repression by REST, in vivo competition experiments were performed. Both repression domains were expressed in the nucleus as fusion proteins with S. japonicum glutathione S-transferase (GST). The ability of these fusion proteins to block transcriptional repression mediated by the repressor domains of REST was tested. The results show that transcriptional repression by the N-terminal repression domain of REST could be overcome by expression of a GST fusion protein encoding the N-terminal, but not C-terminal repression domain, and vice versa, suggesting that both repression domains have to interact with distinct nuclear factors to exhibit biological activity. The GST-REST fusion proteins had no effect upon transcriptional repression mediated by the KRAB (Krüppel-associated box) domain, a strong mammalian repressor domain, or the repressor domain derived from the thyroid hormone receptors alpha. We conclude that REST has to interact with at least two distinct nuclear factors to inhibit transcription. These factors are distinct from the mammalian corepressor proteins KAP-1/KRIP-1 and N-CoR that mediate repression by the KRAB domain or the thyroid hormone receptor alpha. Thus, mammalian transcriptional repressors utilize different mechanisms to inhibit transcription by using different kinds of protein-protein interactions.

Animals↗

The association of resting heart rate with cardiovascular, cancer and all-cause mortality. Eight year follow-up of 3527 male Israeli employees (the CORDIS Study)

BACKGROUND: Resting heart rate has frequently been shown to be a predictor of coronary heart disease mortality. Elevated heart rate could also be a marker for the presence of other risk factors, which have not been taken into consideration in previous studies. OBJECTIVE: To evaluate the effect of resting heart rate on the risk of all-cause cardiovascular and cancer mortality, taking into consideration haematological variables. METHOD: The association between resting heart rate and mortality was assessed applying Cox's proportional hazard models to data obtained in an 8 year follow-up of 3527 Israeli male industrial employees. During this period 135 deaths were recorded, 57 from cardiovascular disease and 45 from cancer. Resting heart rate was assessed at entry; potential confounding demographic, anthropometric and socioeconomic variables, haematological data, serum lipid levels and health-related habits were accounted for. RESULTS: We found that the relative risk of all-cause mortality increased with increasing resting heart rate, workers with resting heart rate >90 beats. min(-1)had an adjusted relative risk of 2.23 (95% CI 1.4-3.6) compared with those with a heart rate <70 beats. min(-1). A similar result was achieved for cardiovascular disease mortality (adjusted relative risk 2.02, 95% CI 1.1-4.0). Cancer mortality was not associated with resting heart rate. CONCLUSION: This study found that resting heart rate is associated with all-cause and cardiovascular disease mortality after controlling (in various statistical models) for platelet counts, haemoglobin concentration, white blood cell counts, total protein, and other recognized risk factors.

Adult↗

Mechanism of myocardial dysfunction in the presence of chronic coronary stenosis and normal resting myocardial blood flow: clinical implications.

In chronic coronary artery disease, resting myocardial dysfunction can exist despite normal resting transmural myocardial blood flow (MBF). We hypothesized that this phenomenon occurs because of diminished endocardial MBF reserve. MBF (measured with radiolabeled microspheres) and wall thickening (WT) (measured with echocardiography) were assessed in 7 dogs after the development of severe left ventricular dysfunction caused by placement of ameroid constrictors on the left anterior descending (LAD) and left circumflex arteries and 3 weeks after selective bypass surgery to the LAD. Before surgery, the mean transmural MBF at rest and at peak dobutamine dose in the LAD bed were 1.1 +/- 0.5 and 3.0 +/- 1.5 mL/min per gram, respectively, and were not significantly changed after LAD bypass. The resting endocardial-to-epicardial MBF ratio (EER) was also normal before bypass (1.5 +/- 0.6) and remained unchanged after surgery. The prebypass EER at peak dobutamine dose, however, was markedly diminished in the LAD bed (0.7 +/- 0.3) and improved significantly (1.3 +/- 0.8, P <.01) after surgery. Resting WT in the LAD bed also improved to normal levels (36% +/- 4% versus 13% +/- 6%, P =.0001) and no longer demonstrated a biphasic response to dobutamine. In comparison, the nonbypassed left circumflex bed continued to show reduced resting WT (12% +/- 6%), a biphasic response to dobutamine, and abnormal EER during rest and dobutamine (0.7 +/- 0.3). We conclude that persistent myocardial dysfunction in the presence of normal resting transmural MBF can occur as a result of diminished endocardial MBF reserve, with transmural MBF reserve remaining normal.

Animals↗

The relations between prepotential, resting potential, and latent period in frog muscle fibers.

1. Prepotentials and action potentials were recorded from amphibian striated muscle fibers. Intracellular electrodes were used for stimulating and recording. The resting potential was varied from 55 to 120 mv. by alterations of the KCl concentration of the Ringer's fluid. The magnitude of the prepotential at the initiation of the spike potential was measured and compared to the resting potential and the latent period (time between stimulus "make" and excitation). The magnitude of this prepotential varied with the resting potential. 2. A large prepotential or cathodal depolarization was required to excite a fiber with a high resting potential. If a fiber with a high resting potential fired late (long latency), the adequate prepotential was larger than if the fiber fired early. Fibers with low resting potentials had smaller adequate prepotentials. Also, the adequate prepotential was independent of the latent period, in these depolarized fibers. 3. If the concentration of Ca(++) was increased tenfold, the adequate prepotential of depolarized fibers became strongly dependent upon the latency. 4. Fibers with large or normal resting potentials were prone to respond repetitively during the passage of long duration shock, whereas depolarized and Ca(++)-treated fibers were not. 5. The so-called critical membrane potential (which is defined as the transmembrane potential at the point of excitation) was not independent of the resting potential.

Action Potentials↗

Resting metabolic rate before exercise vs a control day.

Investigations on resting and recovery metabolism have used both preexercise and separate control-day measurements as a baseline for comparisons. The purpose of this study was to compare preexercise resting data with nonexercise control-day resting data. Seven active men aged 25 +/- 5 y and weighing 83.2 +/- 15.4 kg followed prescribed dietary (12-h fast) and activity (48-h abstinence) preparatory protocols and were scheduled to exercise for 60 min on three separate occasions. A fourth session involved no exercise (control) and included an extended rest period. Resting metabolic rate (RMR) and heart rate measured in a semirecumbent position were not significantly different among preexercise and control conditions. Respiratory exchange ratio (RER) increased as the control rest was extended to 120 min. Reliabilities for both RMR and RER were initially high but were decreased at the end of the extended rest. These results suggest that preexercise RMR data can be used as a baseline for comparison purposes. In addition, prolonging the rest period does not appear to improve the RMR or RER values.

Adult↗

Exercise intensity does not affect depression of resting metabolic rate during severe diet restriction in male Sprague-Dawley rats.

This study examined the effects of high and low intensity exercise on the resting metabolic rate during severe dietary restriction. We hypothesized that exercise would attenuate and/or offset the decline in resting metabolic rate during energy-deficit conditions. Thirty-two male 90-d-old Sprague-Dawley rats were divided into four groups: control, diet restriction only, diet restriction plus high intensity exercise, and diet restriction plus low intensity exercise. The body weights of the diet-restricted groups were rapidly reduced over 5 wk until rats in these three groups weighted 64% of control weight, and this difference in body weight was maintained for the last 5 wk of the study. The high and low intensity exercise groups ran 5 d/wk at 75 and 37.5%, respectively, of maximal running speed for 45 and 90 min/d, respectively. Resting metabolic rate (23-h oxygen uptake) was measured during wk 2, 4, 6, 8 and 10. Resting metabolic rate for the three diet-restricted groups was significantly lower (25-37%) than for the controls for all measurements. Exercise training had no effect on the diet-induced depression of resting metabolic rate, with the diet-restricted groups differing among each other by < 2% during the measurement periods. During severe diet-restriction, exercise-induced elevations of resting metabolic rate seem to be greatly reduced or eliminated. This absence of an exercise effect on resting metabolic rate persisted through 5 wk of reduced body weight maintenance. We conclude that during severe diet restriction, exercise offers no "protective" or enhancing effect on resting metabolic rate.

Animals↗

Peritoneal dialysis fluid-induced changes of the peritoneal membrane are reversible after peritoneal rest in rats.

BACKGROUND: Peritoneal dialysis (PD) is associated with functional and structural alterations of the peritoneal membrane. However, the (ir)reversibility of these pathological changes of the peritoneum is not understood fully. METHODS: In an experimental PD model, rats (n = 15) received daily 10 ml conventional glucose containing PD fluid, via peritoneal catheters connected to implanted subcutaneous mini vascular access ports. After 5 weeks of treatment, the first group of animals (PDF; n = 10) was sacrificed, while peritoneal catheters of the remaining group of rats (PD-rest; n = 5) were removed 1 week later. The latter group (PD-rest) was sacrificed 12 weeks after removing catheters. At both time points, untreated rats were included as controls. Cellular and morphological parameters were analysed by light and electron microscopy. RESULTS: Rats exposed to PD fluid for 5 weeks showed a severe angiogenesis in various peritoneal tissues. Peritoneal rest resulted in a significant reduction in blood vessel density in visceral (mesentery, P<0.05), but not in parietal peritoneum. Five weeks' exposure to PD fluid resulted in a profound fibrosis in the parietal peritoneum, whereas the degree of fibrosis was significantly reduced in the PD-rest group (P<0.02). Daily exposure to PD fluid induced a higher number of mast cells in the omentum compared with untreated rats, whereas peritoneal rest normalized the increased mast cell density completely (P<0.03). Likewise, continued PD fluid instillation evoked a strong omental milky spot response, which was returned to the control level after peritoneal rest (P<0.009). Furthermore, the number of mesothelial cells on the liver was significantly increased in rats treated with PD fluid, whereas animals from the PD-rest group had a lower number of mesothelial cells, although this was not statistically significant (P = 0.08). Finally, as evidenced by electron microscopy, daily exposure to PD fluid resulted in severe damage to the mesothelial cell layer covering the peritoneum, whereas this cell layer was completely recovered after peritoneal rest. CONCLUSIONS: We show that PD fluid-induced cellular and morphological alterations of the peritoneal membrane are generally reversible.

Animals↗

Patterns of neuroendocrine activation at rest and during exercise following acute myocardial infarction.

Previous studies of neurohumoral activation following myocardial infarction have concentrated on the within-hospital phase and have only made measurements at rest. The objectives of this study were to measure neuroendocrine activity in the early convalescent phase of myocardial infarction at rest and during symptom-limited maximal exercise and to study the effects of early drug therapy. We studied 75 patients, mean age 57 (range 37-74) without evidence of overt heart failure, following Q-wave myocardial infarction. Patients were studied a mean of 17 days following myocardial infarction and compared with 11 age-matched control subjects. Plasma noradrenaline, adrenaline, atrial natriuretic peptide and plasma renin activity were measured at rest, at submaximal and symptom-limited maximal treadmill exercise. At the time of study 40 patients were taking beta-blockers, 19 diuretics and 16 no treatment. Atrial natriuretic peptide levels were higher at rest (P = 0.0001) and at symptom-limited exercise (P = 0.002) in the patient group than in the control subjects. Although there were no significant resting differences between the patient subgroups, at symptom-limited exercise plasma atrial natriuretic peptide levels were significantly higher in the patients taking beta-blockers than in the other patient groups (P = 0.001). Plasma renin activity was no different between the patients and the control subjects at rest or during exercise. Those patients taking diuretics had higher values at rest (P = 0.001) and during exercise (P = 0.005) compared with the remaining patients. There were no significant differences in resting or maximal exercise levels of plasma noradrenaline and adrenaline between the patients and the control subjects (all P > 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Painful nerve injury decreases resting cytosolic calcium concentrations in sensory neurons of rats.

BACKGROUND: Neuropathic pain is difficult to treat and poorly understood at the cellular level. Although cytoplasmic calcium ([Ca]c) critically regulates neuronal function, the effects of peripheral nerve injury on resting sensory neuronal [Ca]c are unknown. METHODS: Resting [Ca]c was determined by microfluorometry in Fura-2 AM-loaded neurons dissociated from dorsal root ganglia of animals with hyperalgesia to mechanical stimulation after spinal nerve ligation and section (SNL) at the fifth and sixth lumbar (L5 and L6) levels and from animals after skin incision alone (control group). Axotomized neurons from the L5 dorsal root ganglia were examined separately from adjacent L4 neurons that share the sciatic nerve with degenerating L5 fibers. RESULTS: After SNL, large (34 mum or larger) neurons from the L4 ganglion showed a 29% decrease in resting [Ca]c, whereas those from the L5 ganglion showed a 54% decrease. Small neurons only showed an effect of injury in the axotomized L5 neurons, in which resting [Ca]c decreased by 30%. A decrease in resting [Ca]c was not seen in neurons isolated from rats in which hyperalgesia did not develop after SNL. In separate experiments, SNL reduced resting [Ca]c in capsaicin-insensitive neurons of the L5 ganglion by 60%, but there was no change in neurons from L4. Resting [Ca]c of capsaicin-sensitive neurons was not affected by injury in either ganglion. SNL injury decreased the proportion of neurons sensitive to capsaicin in the L5 group but increased the proportion in the L4 group. CONCLUSIONS: Painful SNL nerve injury depresses resting [Ca]c in sensory neurons. This is most marked in axotomized neurons, especially the large and capsaicin-insensitive neurons presumed to transmit non-nociceptive sensory information.

Animals↗

Production of HIV-1 by resting memory T lymphocytes.

BACKGROUND: The persistence of HIV-1 within resting memory CD4 T cells constitutes a major obstacle in the control of HIV-1 infection. OBJECTIVE: To examine the expression of HIV-1 in resting memory CD4 T cells, using an in-vitro model. DESIGN AND METHODS: Phytohaemagglutinin-activated peripheral blood mononuclear cells were challenged with T cell-tropic and macrophage-tropic HIV-1 clones, and with a replication-incompetent and non-cytotoxic HIV-1-derived vector (HDV) pseudotyped by the vesicular stomatitis virus glycoprotein G. To obtain resting memory CD4 T cells containing HIV-1 provirus, residual CD25(+), CD69(+) and HLA-DR(+) cells were immunodepleted after a 3 week cultivation period. RESULTS: In spite of the resting phenotype, the majority of provirus-harbouring T cells expressed HIV-1 genomes and produced infectious virus into cell-free supernatant. The expression of HDV dropped by only 30% during the return of activated HDV-challenged cells into the quiescent phase. Although resting memory T cells generated in vitro expressed HIV-1 and HDV genome when infected during the course of the preceding T cell activation, they were resistant to HIV-1 and HDV challenge de novo. The infected culture of resting memory T cells showed a higher resistance to the cytotoxic effects of HIV-1 in comparison with the same cultures after reactivation by phytohaemagglutinin. CONCLUSION: The majority of resting memory T cells infected during the course of a preceding cell activation produces virus persistently, without establishing a true HIV-1 latency. The described system could be used as a model for testing new drugs able to control residual HIV-1 replication in resting memory T cells.

CD4-Positive T-Lymphocytes↗