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At least 1,783 records · Page 99Linked to original sources
PubMed1996

Evidence that guanylate cyclase is involved in modulating the resting tension and neurally-induced contraction of the guinea pig tracheal muscle.

Electrical field stimulation of guinea-pig tracheal muscle strips produced a frequency-dependent biphasic response consisting of an initial cholinergic contraction followed by relaxation. Both phases of the response were of neural origin. In the presence of methylene blue, a guanylate cyclase inhibitor, the resting tension and the contraction were increased, but the accompanying relaxation was inhibited. However, in the presence of sodium nitroprusside, a guanylate cyclase activator, the resting tension was reduced and the contraction was inhibited, but the relaxation was prolonged and increased. Similarly, in the presence of either 3-isobutyl-1-methylxanthine, which promotes cyclic guanosine monophosphate (cGMP) accumulation, or 8-bromo-cGMP, an analogue of cGMP, the resting tension was reduced and the contraction was inhibited but the relaxation was prolonged and increased. From these results, it is concluded that guanylate cyclase is involved in modulating the resting tension and the neurally-induced contraction of guinea-pig tracheal muscle.

1-Methyl-3-isobutylxanthine↗
PubMed1996

[Assessment of myocardial viability using 201TL SPECT at rest to predict the reversibility of left ventricular wall motion abnormalities].

AIM: The aim of the present study was to predict preoperatively the reversibility of left ventricular wall motion abnormalities using TI-201 SPECT at rest. METHODS: 19 patients with advanced coronary artery disease and regional wall motion abnormalities were examined at rest with TI 201 SPECT (acquisition 15 minutes and 3 hours post injection). Successfully revascularized, proven by a second coronary angiography three month after revascularisation. Wall motion was again evaluated by cineventriculography. RESULTS: The preoperative a- or dyskinetic segments were best separated by the minimal relative TI-201 uptake in the defect 3 hrs p.i. in (i) postinterventionally improved wall motion (TI-201 uptake 67 +/- 14%, viable) and in (ii) without recovery (TI-201 uptake 46 +/- 12%, p < 0.001, non viable). A threshold at a TI-201 uptake of more than 50% yielded a positive predictive value of 0.73 and a negative predictive value of 0.86. If the segments with wall motion abnormalities (hypokinetic included) were evaluated as one group, no such threshold was obtained all segments which occurred a TI-201 uptake of more than 80% showed a functional recovery, wall motion did not improve in any segment with a TI-201 uptake of less than 40%. In the present study a considerable influence of the defect localisation with regard to the posterior wall was not observed. The values of TI-201 redistribution under resting condition were not useful to predict functional recovery. CONCLUSION: TI-201 SPECT in rest predicts preoperatively the reversibility in regions with severe wall motion abnormalities only and indicates myocardial viability in these cases. Thus, the method is basically useful to determine myocardial viability. In hypokinetic segments, however, a wide range of TL-201 uptake values exists without definite evidence to functional recovery.

Aged↗
PubMed1997

[A calculation of an index of the coronary flow reserve using exercise and rest myocardial SPECT with 99mTc-tetrofosmin].

We designed a new method to evaluate the rate of change of myocardial 99mTc-tetrofosmin (TF) uptake between exercise and rest images with a 1-day protocol. Fifteen normal cases were studied. A 370 MBq of TF was injected at peak exercise. Initial (TF1) and delayed (TF2) exercise SPECT images were acquired 30 min and 3 hr after the injection. A 740 MBq of TF was reinjected soon after TF2 acquisition, and rest SPECT images (TF3) were obtained 30 min after the reinjection. Myocardial counts of TF1, TF2 and TF3 were defined C1, C2 and C3 respectively. Then, the rate of change of myocardial TF uptake between exercise and rest (delta MTU: delta myocardial TF uptake) was determined by the following formula. delta MTU = [(C1/(C3-C2)] x R-1] x 100 (%) (R: dose ratio). delta MTU was 57.8 +/- 9.9% in normal cases and roughly correlated with maximal heart rates and double product. If the extraction fraction of TF is not changed under the exercise and resting condition, delta MTU may have some relation with the coronary flow/cardiac output ratio at exercise. In conclusion, delta MTU is a useful index to evaluate coronary flow reserve non-invasively.

Adult↗
PubMedDate not supplied

Patterns of fatigue and activity and rest during adjuvant breast cancer chemotherapy.

PURPOSE/OBJECTIVES: To describe the patterns of fatigue and activity and rest and their relationship during adjuvant breast cancer chemotherapy. DESIGN: Prospective, descriptive, repeated measures. SETTING: Midwestern oncology clinics and subjects' homes. SAMPLE: 72 women, ages 30-69, who were receiving chemotherapy after surgery for stage I or II breast cancer. METHODS: The Piper Fatigue Scale was used to measure fatigue 48 hours after each treatment and at treatment cycle midpoints for three cycles. Wrist actigraphs were used to measure activity and rest cycles for 96 hours at each treatment and for 72 hours at each cycle midpoint. MAIN RESEARCH VARIABLES: Fatigue, activity and rest cycles, chemotherapy protocols (doxorubicin- or non-doxorubicin-based protocols). FINDINGS: Total and subscale fatigue scores were significantly different over time, with scores higher at treatments and lower at cycle midpoints. Activity levels were significantly different over time in a mirror-image pattern of fatigue. Fatigue was negatively correlated with activity levels at all times except the cycle 2 midpoint and positively correlated with awakenings at night only at the cycle 2 midpoint. Activity levels were significantly lower in women receiving doxorubicin-based protocols. CONCLUSIONS: Roller-coaster patterns of fatigue and activity have not been previously reported in this patient population. Examination of the inverse relationship between fatigue and activity will assist nurses in the development and testing of interventions to modify fatigue. IMPLICATIONS FOR NURSING PRACTICE: Women should be instructed to monitor the intensity of fatigue and encouraged to maintain activity levels balanced with efficient rest periods. Nurses can inform women that these patterns may be expected to be similar during the first three chemotherapy cycles.

Activity Cycles↗
PubMed1998

[The utility of various Doppler parameters at rest and during exercise for the diagnosis of residual stenosis after operation for aortic coarctation. A doppler-nuclear magnetic resonance comparison].

BACKGROUND: The postoperative follow-up of aortic coarctation (AoCo) is often characterized by persistent arterial hypertension, sometimes due to a residual narrowing at the site of surgical repair. A residual stenosis > or = 30% is considered to be significant. Anatomy of the aortic arch is best assessed by angiography, transesophageal echocardiography and magnetic resonance imaging (MRI). The use of these invasive and expensive procedures for routine examination in all patients who develop late systemic hypertension cannot be justified. Consequently, it would appear to be useful to find some noninvasive methods, such as Doppler gradients, that are capable of identifying any residual anatomic narrowing. OBJECTIVES: We compared different Doppler parameters obtained at rest and during exercise with the degree of narrowing at the site of surgical repair measured by MRI, in order to identify the indices predictive of residual stenosis. METHODS: Thirty-nine patients (26 M, 13 F) were studied after AoCo repair. Mean age was 21.7 +/- 9.7 years (9-49). Their age at the time of repair was 10 +/- 9.7 years (0.1-27) and the postoperative follow-up was 11.5 +/- 6 years (2-25). Systolic blood pressure measurement and Doppler echo for calculation of the transisthmic gradient at rest and during exercise on a bicycle ergometer were performed in all patients. The peak systolic gradient (PGs) over the isthmus was calculated using the simplified Bernoulli equation: PGs = 4 x (V2(2)-V1(2)), where V1 and V2 are the peak velocities in the ascending and descending aorta. In addition, at the end of exercise the peak diastolic gradient (PGd) was measured at the end of the T wave on the ECG, and the systolic velocity half-time (SVHT), as the time interval from the peak to the half peak systolic velocity. MRI of the aorta was performed to measure the diameter of the isthmus (AI) and of the descending aorta at the diaphragm (DA). Residual narrowing at the isthmus was expressed as stenosis % = [(1-(AI/DA)]%. RESULTS: At rest: systolic blood pressure 128.3 +/- 22.5 mmHg, PGs 15.9 +/- 8.1 mmHg (1-32). None of the patients had PGd. At peak exercise: systolic blood pressure 207 +/- 37 (160-265) mmHg, PGs 32.3 +/- 14.7 mmHg (8-70), SVHT 96 +/- 23 msec (60-139) and PGd 7.2 +/- 4.8 mmHg (1-17). Stenosis % measured by MRI was 23.1 +/- 14.5% (0-53) and in particular, it was < 30% in 25 patients and > or = 30% in 14 patients. Both the PGs at rest and the other Doppler parameters at peak exercise (PGs, SVHT, PGd) correlated with stenosis %. SVHT together with PGd on exercise Doppler represented the combination of two variables that was best for predicting a residual stenosis. When all three variables obtained by exercise Doppler were combined, every patient with residual stenosis was correctly identified. In particular, the combination (PGs > or = 28 mmHg + SVHT > or = 108 msec + PGd > or = 8 mmHg) identifies all patients with stenosis > or = 30%, while the combination (PGs < or = 38 mmHg + SVHT < 108 msec + PGd < 10 mmHg) excluded those with significant stenosis. CONCLUSION: Parameters obtained from the transisthmic gradient (PGs, SVHT, PGd) measured at peak exercise by CW-Doppler can diagnose a residual stenosis % in operated AoCo. We propose using this noninvasive method of identifying patients who need to be referred for MRI.

Adolescent↗
PubMed1998

Resting muscle sympathetic nerve activity does not predict duration of symptom-limited submaximal exercise in young patients with dilated cardiomyopathy.

OBJECTIVE: To determine whether increased sympathetic vasoconstrictor drive to the calf in heart failure is associated with reduced symptom-limited submaximal exercise performance. DESIGN: Blood pressure, heart rate and peroneal muscle sympathetic nerve activity (MSNA) were recorded during rest and before symptom-limited treadmill exercise at 70% of resting heart rate reserve for up to 45 mins. PATIENTS: Thirteen young patients with dilated cardiomyopathy (age 36 +/- 2 years). RESULTS: MSNA (45 +/- 6 bursts/min) was more than double the level documented in an age-, sex- and weight-matched group of normal subjects studied under identical baseline conditions. Patients with ventricular dysfunction exercised for 30 +/- 3 mins on average, but exercise distance and duration were independent of resting MSNA. CONCLUSIONS: In young patients with dilated cardiomyopathy, sympathetic nerve traffic to the calf vascular bed, measured at rest, does not predict the distance or duration of symptom-limited submaximal treadmill exercise.

Adult↗
PubMed1998

Plasma volume expansion with oral fluids in hypohydrated men at rest and during exercise.

BACKGROUND: The purpose for this study was to evaluate various carbohydrate (CHO)-electrolyte fluid formulations for consumption by astronauts to maintain or restore their plasma volume (PV) and total body water (TBW) during and after extravehicular activity (exercise experiment, EE) and for a few hours before reentry and immediately after landing (rest experiment RE). HYPOTHESIS: That fluid formulation electrolyte content would be more important than osmotic (Osm) content for increasing or maintaining PV during the RE and EE. METHODS: In the RE, 5 healthy men (23-44 yr), previously dehydrated for 24 h, drank 6 fluid formulations (Water, 19.6 Na, 157 Na, 19.6 Na + glucose, and the prepared drinks Performances and Power)--one each at weekly intervals, and then sat for 70 min. In the EE, four healthy 24-h dehydrated men (30-46 yr) exercised for 70 min supine on a cycle ergometer (load = 71 +/- 1% peak VO2). RESULTS: Rest: Subjects who consumed formulations with total Osm concentrations nearer the normal range (157 Na - 270 mOsm x kg(-1), Performance with 19.6 mEq x L(-1) Na - 380 mOsm, and to some extent Power with 23.5 mEq x L(-1) Na - 390 mOsm) had the greater increases in PV; intake of drink 157 Na, with the largest Na content, induced the greatest hypervolemia of 7.6% (p < 0.05). The various additional ions, in addition to 19.6 Na, probably contributed to the 4.6% (p < 0.05) hypervolemia with Performance. Water was not effective. Exercise: Stabilization of PV between 15-70 min was not related to drink total CHO, Na or Osm content. Performance and 157 Na were no more effective than 19.6 Na or 19.6 Na + glu for PV stabilization. Water was the least effective. Regulatory mechanisms controlling PV during exercise appear to be independent of oral fluid formulation Osm-electrolyte content. CONCLUSIONS: Drink cation (sodium) content is more important that its total osmotic content for increasing plasma volume at rest. Fluid formulations with greater hypervolemic action in resting subjects may not be as effective during exercise; therefore different formulations for use during exercise appear to be necessary.

Adult↗
PubMed1998

Sympathetic activity in patients with panic disorder at rest, under laboratory mental stress, and during panic attacks.

BACKGROUND: The sympathetic nervous system has long been believed to be involved in the pathogenesis of panic disorder, but studies to date, most using peripheral venous catecholamine measurements, have yielded conflicting and equivocal results. We tested sympathetic nervous function in patients with panic disorder by using more sensitive methods. METHODS: Sympathetic nervous and adrenal medullary function was measured by using direct nerve recording (clinical microneurography) and whole-body and cardiac catecholamine kinetics in 13 patients with panic disorder as defined by the DSM-IV, and 14 healthy control subjects. Measurements were made at rest, during laboratory stress (forced mental arithmetic), and, for 4 patients, during panic attacks occurring spontaneously in the laboratory setting. RESULTS: Muscle sympathetic activity, arterial plasma concentration of norepinephrine, and the total and cardiac norepinephrine spillover rates to plasma were similar in patients and control subjects at rest, as was whole-body epinephrine secretion. Epinephrine spillover from the heart was elevated in patients with panic disorder (P=.01). Responses to laboratory mental stress were almost identical in patient and control groups. During panic attacks, there were marked increases in epinephrine secretion and large increases in the sympathetic activity in muscle in 2 patients but smaller changes in the total norepinephrine spillover to plasma. CONCLUSIONS: Whole-body and regional sympathetic nervous activity are not elevated at rest in patients with panic disorder. Epinephrine is released from the heart at rest in patients with panic disorder, possibly due to loading of cardiac neuronal stores by uptake from plasma during surges of epinephrine secretion in panic attacks. Contrary to popular belief, the sympathetic nervous system is not globally activated during panic attacks.

Adrenal Medulla↗
PubMed1987

Resting energy expenditure of host and tumor is similar in rats with methylcholanthrene-induced sarcoma.

In the present study we assessed the resting energy expenditure of 30 free-feeding control and methylcholanthrene-induced sarcoma-bearing rats prior to and following surgical removal of the tumor. Tumor-bearing rats demonstrated carcass wasting and massive tumor growth. The resting energy expenditure data in our model suggest that neither the presence and growth of a tumor nor its removal significantly change resting energy expenditure beyond the normal range for non-tumor-bearing rats. We suggest that in the partition of energy costs between host and tumor, both carry a similar input, proportional to their relative weight, into the total combined resting energy expenditure of host and tumor.

Animals↗
PubMed1996

Cardiovascular function during rest and exercise in patients with sickle-cell anemia and coexisting alpha thalassemia-2.

Cardiac function was measured at rest and during exercise in 9 patients with sickle-cell anemia (SS) and coexisting homozygous alpha thalassemia-2 (alpha thal-2). Results were compared with 18 sickle cell patients with normal alpha globin genes, who were matched to the study group by age, gender, and size, and to published normal values. SS alpha thal-2 patients were less anemic: 9.9 +/- 1.0 vs 8.2 +/- 1.2 gm/dl for SS alone (P<.05). Left ventricular dimensions were normal in SS alpha thal-2 (4.9 +/- 0.7 cm), but increased in SS (5.4 +/- 0.7, cm P=.05) (normal range, 3.7-5.6 cm). Left ventricular wall thickness was, however, dramatically increased in the SS alpha thal-2 patients (free wall, 1.8 +/- 0.6 cm; septum, 1.6 +/- 0.4 cm), though SS controls had normal wall thickness (free wall, 1.0 +/- 0.2 cm; septum, 1.0 +/- 0.2 cm, P<.001) (normal range, 0.6-1.1 cm). At rest, Doppler indices of systolic function were not significantly different between sickle groups and normal values. SS alpha thal-2 patients did have abnormal diastolic filling at rest, as evidenced by a reduced ratio of early/late diastolic filling, 1.4 +/- 0.3 vs. 2.0 +/- 0.5 for SS controls (P<.01), and 1.8 +/- 0.4 for normals. An analysis of covariance suggested that this abnormality persisted after taking into account the previously demonstrated hypertrophy. During exercise, SS alpha thal-2 patients had higher heart rates and blood pressures than SS controls in spite of performing the same or less work. This resulted in a higher double product (an estimate of oxygen consumption) in SS alpha thal-2 patients (37,470 +/- 2,310 mm Hg-BPM) than in SS controls (33,310 +/- 1,490 mm Hg-BPM, P<.01). Work capacity, peak heart rate, and blood pressure were all abnormally decreased in both sickle-cell groups when compared to normal. Cardiac abnormalities noted at rest and during exercise in SS alpha thal-2 patients suggest a role of microvascular occlusion and a protective effect of decreased hemoglobin.

Adult↗
PubMed1997

Bilaterally multicentric synchronous Wilms' tumor: successful conservative treatment despite persistence of nephrogenic rests.

We report a case of synchronous bilateral Wilms' tumor in a girl with incomplete Beck-with-Wiedemann syndrome and hemihypertrophy. Multiple small tumors were present in both kidneys. The initial diagnostic biopsy showed stage I monophasic blastematous Wilms' tumor of favorable histology, with multiple perilobar nephrogenic rests (nephroblastomatosis). By flow cytometry, tumor was diploid, with an S-phase fraction of 13.9%. Dactinomycin and vincristine were begun as per the National Wilms' Tumor Study IV (18 week course). After 1 month, only a single small lesion was evident, which persisted unchanged. Excisional biopsy 5 months after beginning chemotherapy showed entirely necrotic tumor but apparently unaltered nephrogenic rests. After completing chemotherapy, the child has done well, with normal renal function and no evidence of disease 3 years after diagnosis. Management of stage V Wilms' tumor is tailored to the individual case, being as conservative as possible to spare renal parenchyma. Given the high incidence of coexisting nephrogenic rests in bilateral Wilms' tumor, careful follow-up is required, as these potentially premalignant rests may resist chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Association between low birthweight and high resting pulse in adult life: is the sympathetic nervous system involved in programming the insulin resistance syndrome?

To test the hypothesis that elevated sympathetic nervous system (SNS) activity could be determined in utero and be one of the processes mediating the link between size at birth and insulin resistance and raised blood pressure in adult life, we have studied the resting pulse rate of 449 men and women aged 46 to 54 (mean 50) years born in Preston, Lancashire, England whose birth size was recorded in detail. The subjects were visited at home by trained fieldworkers who measured resting pulse rate and blood pressure using an automated recorder. The resting pulse rate ranged from 44 to 108 (mean 73) beats min(-1). It rose with increasing body mass index (r = 0.14, p = 0.003) and waist to hip ratio (adjusted for sex r = 0.10, p = 0.003) and correlated significantly with systolic and diastolic blood pressures (p = 0.001), fasting glucose (p = 0.02), split proinsulin (p = 0.001), and triglyceride concentrations (p = 0.02). The pulse rate fell progressively from 76 beats min(-1) among subjects who weighed 5.5 lb (2.5 kg) or less at birth to 71 beats min(-1) among those who weighed 7.5 lb (3.3 kg) or more (decline in pulse rate per kg increase in birthweight = 2.7, 95 % CI 0.6 to 4.8 beats min(-1). The association was independent of current body mass index, waist to hip ratio and of potential confounding variables including smoking, alcohol consumption, and social class. Although the resting pulse rate is an imperfect index of SNS activity, these findings are consistent with the hypothesis that elevated SNS activity established in utero is one mechanism linking small size at birth with the insulin resistance syndrome in adult life.

Adult↗
PubMed2000

Altered regulation of pyruvate kinase or co-overexpression of phosphofructokinase increases glycolytic fluxes in resting Escherichia coli.

Glycolytic fluxes in resting Escherichia coli were enhanced by overexpression of heterologous pyruvate kinases (Pyk) from Bacillus stearothermophilus and Zymomonas mobilis, but not homologous Pyk. Compared to the control, an increase of 10% in specific glucose consumption and of 15% in specific ethanol production rates was found in anaerobic resting cells, expressing the heterologous Pyks, that were harvested from exponentially growing aerobic cultures. A further increase in glycolytic flux was achieved by simultaneous overexpression of E. coli phosphofructokinase (Pfk) and Pyk with specific glucose consumption and ethanol production rates of 25% and 35% greater, respectively, than the control. Fluxes to lactate were not significantly affected, contrary to previous observations with resting cells harvested from anaerobically growing cultures. To correlate the physiology of resting cells with the physiology of cells prior to harvest, we determined the relevant growth parameters from aerobic and anaerobic precultures. We conclude that glycolytic fluxes in E. coli with submaximal (aerobic) metabolic activity can be increased by overexpression of pyruvate kinases which do not require allosteric activation or co-overexpression with Pfk. However, such improvements require more extensive engineering in E. coli with near maximal (anaerobic) metabolic activity.

Escherichia coli↗
PubMed1996

Percutaneous transluminal angioplasty of internal mammary arteries in patients with rest angina.

Angioplasty of the internal mammary artery (IMA) bypass graft has been shown to be a safe and effective revascularization procedure. However, angiographic and long term clinical outcomes in the high-risk group of patients presenting with rest angina has not been well documented. We report the results of IMA angioplasty in 20 patients with rest angina out of 614 (3.2%) who received a left IMA graft at our institution between April 1987 and September 1994. All patients were admitted with rest angina, 12 patients demonstrated persistent ischemia despite medical therapy, two patients were in heart failure, and one patient was in cardiogenic shock. Balloon angioplasty was successful in 15 of 20 patients (75%). Failed angioplasty was associated with either severe IMA tortuousity (three patients) or inability to cross the anastomotic stenosis with the guide wire (two patients). Each of these five patients required angioplasty of either the native left anterior descending artery or other saphenous vein grafts for clinical stabilization. No patient suffered a major complication (myocardial infarction, emergent coronary bypass surgery, death). Clinical follow-up was obtained in all 20 patients (6 months, 7 years, mean 27 months). Twelve patients (60%) were asymptomatic or had stable angina at follow-up, and 8 returned with anginal symptoms. Four patients required repeat angioplasty for disease in other vessels, two were treated medically for angina, one underwent repeat CABG, and cardiac transplantation was performed in one patient for refractory heart failure. Angiographic follow up was obtained in 10/15 (66%) successful angioplasty patients, and only one patient demonstrated restenosis at the treated site (10%). During follow up one patient developed an IMA stenosis at a previous dissection site in the body of the graft that was treated with angioplasty. These results suggest that IMA angioplasty in patients with rest angina is associated with excellent long term patency and clinical efficacy, as well as low procedural risk.

Adult↗
PubMed1998

Experimental muscle pain does not cause long-lasting increases in resting electromyographic activity.

The mutual links between muscle pain and resting electromyographic (EMG) activity are still controversial. This study described effects of experimental muscle pain on resting EMG activity in a jaw-closing muscle and a leg muscle. Pain was induced by injections of hypertonic saline into the muscles in 10 subjects. Injections of isotonic saline served as a control. The pain intensity was scored on visual analog scales (VAS) and surface and intramuscular wire EMGs were obtained from the resting muscles before, during, and after saline injections. EMG activity was analyzed in 30-s intervals and demonstrated, in both muscles, significant increases 30-60 s after injection of hypertonic saline, but not after injection of isotonic saline. In contrast to the transient increase in EMG activity, the pain sensation lasted up to 600 s after injection of hypertonic saline. It was concluded that acute muscle pain is unable to maintain longer-lasting resting muscle hyperactivity.

Adult↗
PubMed2000

Characterization of prostaglandin E(2) receptors and their role in 24,25-(OH)(2)D(3)-mediated effects on resting zone chondrocytes.

Resting zone chondrocyte differentiation is modulated by the vitamin D metabolite, 24,25-(OH)(2)D(3), via activation of protein kinase C (PKC). In previous studies, inhibition of prostaglandin production with indomethacin caused an increase in PKC activity, suggesting that changes in prostaglandin levels may mediate the 24, 25-(OH)(2)D(3)-dependent response and act as autocrine or paracrine regulators of chondrocyte metabolism. Supporting this hypothesis is the fact that resting zone cells respond directly to prostaglandin E(2) (PGE(2)). The aim of the present study was to identify which PGE(2) receptor subtypes (EP) mediate the effects of PGE(2) on resting zone cells. Using primers specific for EP1-EP4, reverse transcription-polymerase chain reaction (RT-PCR) amplified EP1 and EP2 cDNA in a RT-dependent manner. A variant form of the EP1 cDNA, EPlv, was also amplified in an RT-dependent manner. In parallel experiments, we used EP subtype-specific agonists to examine the role of EP receptors in 24,25-(OH)(2)D(3)-mediated cell proliferation and differentiation. 17-phenyl-trinor-PGE(2) (PTPGE(2)), an EP1 agonist, increased [(3)H]-thymidine incorporation in a dose-dependent manner and reversed the 24, 25-(OH)(2)D(2)-induced inhibition of [(3)H]-thymidine incorporation. SC-19220, an EP1 antagonist, caused a further dose-dependent decrease in 24,25-(OH)(2)D(3)-induced inhibition of [(3)H]-thymidine incorporation. PTPGE(2) also caused a biphasic increase in [(35)S]-sulfate incorporation and increased alkaline phosphatase enzyme activity at high concentrations (10(-8) M). 24, 25-(OH)(2)D(3)-induced alkaline phosphatase activity was synergistically stimulated in a dose-dependent manner by PTPGE(2). In contrast, 24,25-(OH)(2)D(3)-induced PKC activity was inhibited in a dose-dependent manner by PTPGE(2) and SC-19220, the EP1 antagonist, elevated PKC activity at high concentrations (10(-8) M). The EP2 agonist, misoprostol, only affected [(35)S]-sulfate incorporation, but in a dose-dependent manner. The EP3 and EP4 agonists had no effect on cell response. These results suggest that the EP1 receptor subtype mediates some of the PGE(2)-induced cellular responses in resting zone cells that lead to both increased proliferation and differentiation. Because 24,25-(OH)(2)D(3) inhibits PGE(2) synthesis in these cells, EP1-mediated induction of proliferation is blocked, encouraging cellular maturation and activation of PKC activity.

24,25-Dihydroxyvitamin D 3↗
PubMed1997

Resting potential of rat cerebellar granule cells during early maturation in vitro.

The survival of rat cerebellar granule cells maintained in vitro is enhanced by a KCl-enriched medium. This effect is classically interpreted as resulting from a higher cytosolic calcium concentration. This implies the presence of voltage-dependent Ca2+ channels and a membrane potential that can respond to changes in external K+. Since previous studies cast a doubt on these two conditions, we reinvestigated the resting membrane potential and Ca2+ influxes in rat cerebellar granule neurones during the first week in vitro using a fluorescence imaging approach. Membrane potential was assessed with the fluorescent dye bis-oxonol, and intracellular free calcium with Fura-2. Resting potential was shown to progressively decrease from -40 mV at the first day in vitro to -60 mV at day 7. At all times in culture, as early as day 0, cells were depolarized when external KCl concentration was increased from 5 to 30 mM. This depolarization resulted in an increased cytosolic calcium concentration due to Ca2+ influx through L-type and N-type voltage-activated Ca2+ channels, functional at day 0. Gross estimations of the permeabilities of Na+ and Cl- were obtained at various times in culture by measuring the changes in resting potential brought about by a reduction of their external concentration. A progressive increase of the relative permeability to K+ ions seems to underlie the evolution of the resting potential with time.

Animals↗
PubMedDate not supplied

Simultaneous assessment of flow and BOLD signals in resting-state functional connectivity maps.

We have recently demonstrated using functional magnetic resonance imaging the presence of synchronous low-frequency fluctuations of signal intensities from the resting human brain that have a high degree of temporal correlation (p < 0.0001) both within and across the sensorimotor cortex. A statistically significant overlap between the resting-state functional connectivity map and the task-activation map due to bilateral finger tapping was obtained. Similar results have been obtained in the auditory and visual cortex. Because the pulse sequence used for collecting data was sensitive to blood flow and blood oxygenation, these low-frequency fluctuations of signal intensity may have arisen from variations of both. The objective of this study was simultaneously to determine the contribution of the blood oxygenation level signal and the flow signal to physiological fluctuations in the resting brain using the flow-sensitive alternating inversion recovery pulse sequence. In all subjects, the functional connectivity maps obtained from BOLD had a greater coincidence with task-activation maps than the corresponding functional connectivity maps obtained from blood-flow signals at the same level of statistical significance. Results of this study suggest that while variations in blood flow might contribute to functional connectivity maps, BOLD signals play a dominant role in the mechanism that gives rise to functional connectivity in the resting human brain.

Adolescent↗