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Biomedical subjects

D A Schneider

Publications and source records attributed to D A Schneider.

At least 19 recordsLinked to original sources

RNA polymerase II elongation factors Spt4p and Spt5p play roles in transcription elongation by RNA polymerase I and rRNA processing.

Previous investigations into the mechanisms that control RNA Polymerase (Pol) I transcription have primarily focused on the process of transcription initiation, thus little is known regarding postinitiation steps in the transcription cycle. Spt4p and Spt5p are conserved throughout eukaryotes, and they affect elongation by Pol II. We have found that these two proteins copurify with Pol I and associate with the rDNA in vivo. Disruption of the gene for Spt4p resulted in a modest decrease in growth and rRNA synthesis rates at the permissive temperature, 30 degrees C. Furthermore, biochemical and EM analyses showed clear defects in rRNA processing. These data suggest that Spt4p, Spt5p, and, potentially, other regulators of Pol I transcription elongation play important roles in coupling rRNA transcription to its processing and ribosome assembly.

Chromosomal Proteins, Non-Histone↗

Ventilatory and gas-exchange responses to incremental exercise performed with reduced muscle glycogen content.

This study examined the relationship between minute ventilation (VE), CO2 production (VCO2), and blood lactate concentration ([La-]) during incremental exercise performed with reduced muscle glycogen stores. Nine untrained female subjects (25.3+/-4.2 year) performed incremental cycling in a normal glycogen (NG) state and under conditions of reduced muscle glycogen (RG) content. To reduce muscle glycogen stores, subjects cycled to exhaustion (124+/-33 min) at a power output corresponding to their gas-exchange anaerobic threshold. Peak oxygen uptake (VO2peak) was unchanged with glycogen reduction, even though subjects achieved a significantly lower maximal power output in the RG state (p<0.05). Peak blood [La-] decreased significantly by 37% in the RG state (p<0.001). At any percentage of VO2peak, O2 uptake and VE were similar for both treatment conditions, whereas VCO2 and respiratory exchange ratio values were lower during the RG trial than under NG conditions. Therefore, VE/VCO2 tended to be higher and end-tidal CO2 partial pressure tended to be lower during exercise performed in the RG state. VE was significantly correlated with VCO2 under both treatment conditions (NG: r=0.99, p<0.01; RG: r=0.99, p<0.01). However, the slope of the VE-VCO2 relationship was significantly elevated during the RG trial (p<0.01). VE during exercise was similar under both treatment conditions, even though VCO2 and blood [La-] were lower during the RG trial compared to the NG trial. This suggests that factors other than CO2 delivery to the lung and metabolic acidosis play an important role in regulating VE during exercise.

Adult↗

Expression of sodium channel Nav1.6 in cholinergic myenteric neurons of guinea pig proximal colon.

We wished to establish the functional identity of Na(v)1.6-expressing myenteric neurons of the guinea pig proximal colon by determining the extent of colocalization of Na(v)1.6 and selected neurochemical markers. Na(v)1.6-like immunoreactivity (-li) was primarily localized to the hillock and initial segments of myenteric neurons located near junctions with internodal fiber tracts. Immunoreactivity for Na(v)1.6 was co-localized with choline-acetyltransferase-li, representing 96% of Na(v)1.6-immunoreactive neurons; about 5% of these neurons showed co-localization with calretinin-li, but none with substance-P-li. Cholinergic neurons expressing Na(v)1.6 were amongst the smallest (somal area <300 mum(2)) of all cholinergic myenteric neurons observed. Only three of 234 Na(v)1.6-immunoreactive neurons exhibited nNOS-li, and none co-localized with calbindin-li. These data suggest that Na(v)1.6 is expressed in a small uniform population of cholinergic myenteric neurons that lie within the guinea pig proximal colon and that are likely to function as excitatory motor neurons.

Animals↗

Expression of the sodium channel Na(v)1.2 in chemically identified myenteric neurons in the guinea pig.

Our purpose was to identify Na(v)1.2-expressing myenteric neurons of the small and large intestine of the guinea pig by using antibodies directed against Na(v)1.2 and selected neurochemical markers. Na(v)1.2-like immunoreactivity (-li) co-localized with immunoreactivity for choline acetyltransferase in all regions, representing 45%-67% of Na(v)1.2-positive neurons. Na(v)1.2-li co-localized with immunoreactivity for the neural form of nitric oxide synthase more frequently in the colon (20% of neurons exhibiting Na(v)1.2-li) than in the ileum (8%). Co-localization of Na(v)1.2-li with immunoreactivity for a form of neurofilament (NF145) was infrequently observed in the ileum and colon. Enkephalin-immunoreactive cell bodies co-localized with Na(v)1.2-li in all regions. Few myenteric cell bodies immunoreactive for neuropeptide Y were observed in the ileum, but all co-localized with Na(v)1.2-li. This and our previous data suggest that Na(v)1.2 is widely expressed within the guinea pig enteric nervous system, including the three main classes of myenteric neurons (sensory, motor, and interneurons), and is involved in both excitatory and inhibitory pathways. Notable exceptions include the excitatory motor neurons to the longitudinal smooth muscle, the ascending interneurons of the ileum, and the myenteric neurons immunoreactive for NF145, few of which are immunoreactive for Na(v)1.2.

Animals↗

Continuous and intermittent exercise responses in individuals with chronic obstructive pulmonary disease.

BACKGROUND: While the acute physiological responses to continuous exercise have been well documented in individuals with chronic obstructive pulmonary disease (COPD), no previous study has examined the response to intermittent exercise in these patients. METHODS: We examined the physiological responses of 10 individuals with moderate COPD (forced expiratory volume in 1 second 52 (15)% predicted) who performed both an intermittent (1 min exercise and rest intervals) and a continuous cycle ergometer test on separate days. Both intermittent and continuous exercise tests were performed at the same power output, calculated as 70% of the peak power attained during an incremental exercise test. RESULTS: Intermittent exercise was associated with significantly lower values for oxygen uptake, carbon dioxide output, expired ventilation, heart rate, plasma lactate concentration, and ratings of breathlessness than continuous exercise. Subjects were able to complete a significantly greater total amount of work during intermittent exercise (71 (32) kJ) than during continuous exercise (31 (24) kJ). The degree of dynamic lung hyperinflation (change in end expiratory lung volume) was significantly lower during intermittent exercise (0.23 (0.07) l) than in continuous exercise (0.52 (0.13) l). CONCLUSIONS: The greater amount of work performed and lower measured physiological responses achieved with intermittent exercise may allow for greater peripheral training adaptations in individuals with more limited lung function. The results suggest that intermittent exercise may be superior to continuous exercise as a mode of training for patients with COPD.

Aged↗

Effect of ramp slope on ventilation thresholds and VO2peak in male cyclists.

This study investigated the effect of 10 W*min(-1) (Slow ramp, SR), 30 W*min(-1) (Medium ramp, MR) and 50 W*min(-1) (Fast ramp, FR) exercise protocols on assessments of the first (VT1) and second (VT2) ventilation thresholds and peak oxygen uptake (VO(2)peak) in 12 highly-trained male cyclists (mean +/- SD age = 26 +/- 6 yr). Expired gas sampled from a mixing chamber was analyzed on-line and VT1 and VT2 were defined as two break-points in 20-s-average plots of pulmonary ventilation (V(E)), ventilatory equivalents for O(2) (V(E)/VO(2)) and CO(2) (V(E)/VCO(2)), and fractions of expired O(2) (F(E)O(2)) and CO(2) (F(E)CO(2)). Arterialized-venous blood samples were analyzed for blood-gas and acid-base status. VO(2)peak was significantly lower (p < 0.05) for SR (4.65 +/- 0.53 l small middle dot min(-1)) compared to MR (4.89 +/- 0.56 l *min(-1)) and FR (4.88 +/- 0.57 l *min(-1)) protocols. CO(2) output and blood PCO(2) were lower (p < 0.05), and V(E)/VCO(2) was higher (p < 0.05), above VT1 for SR compared to MR and FR protocols. No significant differences were observed among the protocols for VO(2), % VO(2)peak, V(E), plasma lactate ([La(-)]) and blood hydrogen ion concentration ([H(+)]), and heart rate (HR) values at VT1 or VT2. The work rate (WR) measured at VT1, VT2 and VO(2)peak increased (p < 0.05) with steeper ramp slopes. It was concluded that, in highly-trained cyclists, assessments of VT1 and VT2 are independent of ramp rate (10, 30, 50 W*min(-1)) when expressed as VO(2), % VO(2)peak, V(E), plasma [La(-)], blood [H(+)] and HR values, whereas VO(2)peak is lower during 10 W*min(-1) compared to 30 and 50 W*min(-1) ramp protocols. In addition, the WR measured at VT1, VT2 and VO(2)peak varies with the ramp slope and should be utilized cautiously when prescribing training or evaluating performance.

Adult↗

Reliability of MAOD measured at 110% and 120% of peak oxygen uptake for cycling.

PURPOSE: The purpose of this study was to examine the test-retest reliability of maximal accumulated oxygen deficit (MAOD) measured at 110% and 120% of peak oxygen uptake (VO2) for cycling in seven untrained male and seven untrained female subjects. METHODS: After one familiarization trial, all subjects performed two MAOD tests at a power output corresponding to 110% and two tests at 120% of VO2peak in random order. MAOD was calculated for each subject as the difference between O2 demand during exercise and the measured VO2. RESULTS: The mean (+/-SEM) time to exhaustion for the group was not significantly different between trial 1 (226 +/- 13 s) and trial 2 (223 +/- 14 s) of the 110% test. Likewise, the difference in the time to exhaustion between trial 1 (158 +/- 11 s) and trial 2 (159 +/- 10 s) was not significant for the 120% test. The intraclass correlation coefficients for the time to exhaustion were 0.95 for the 110% test and 0.98 for the 120% test. The mean MAOD value obtained in trial 1 (2.62 +/- 0.17 L) was not significantly different from the mean value obtained in trial 2 (2.54 +/- 0.19 L) for the 110% test. Additionally, the mean values for the two trials did not differ significantly for MAOD (2.64 +/- 0.21 L for trial 1 and 2.63 +/- 0.19 L for trial 2) in the 120% test. The intraclass correlation coefficients for MAOD were 0.95 for the 110% test and 0.97 for the 120% test. All intraclass correlation coefficients were significant at P < 0.001. CONCLUSIONS: When conducted under standardized conditions, the determination of MAOD for cycling was highly repeatable at both 110% and 120% of VO2peak in untrained male and female subjects.

Adult↗

Functional properties of heteromeric P2X(1/5) receptors expressed in HEK cells and excitatory junction potentials in guinea-pig submucosal arterioles.

P2X receptors are ATP-gated cation channels; they form as homomers or heteromers from a family of seven related subunits. In particular, heteromeric channels comprising P2X(2) and P2X(3) subunits, or P2X(1) and P2X(5) subunits, show distinctive physiological and pharmacological properties in heterologous expression systems. There is substantial evidence that one of the native P2X receptors in sensory neurones corresponds to the P2X(2/3) heteromer, but there is no evidence for P2X(1/5) heteromers in native tissue. We recorded currents in response to activation of heteromeric P2X(1/5) receptors expressed in HEK293 cells to characterize further their functional properties. The ATP concentration-response curve had a threshold concentration of 1 nM, and a Hill slope of one. TNP-ATP was a weak partial agonist, and a non-competitive antagonist which inhibited maximal ATP currents by 60%. Increasing or decreasing pH from 7.3 shifted the ATP concentration-response curves to the right by fivefold and decreased the maximum current by 40%. Calcium permeability was lower than that observed for other P2X receptors (P(Ca)/P(Na) ratio=1.1). The nanomolar sensitivity of this receptor revealed a steady release of ATP from HEK293 cells, providing an extracellular concentration which ranged from 3 to 300 nM. Noradrenaline (0.3-30 microM) increased ATP-evoked currents by 35%; this facilitation occurred within 20 ms. We also recorded excitatory junction potentials (EJPs) from guinea-pig submucosal arterioles. EJPs were inhibited by suramin and PPADS (IC(50)s of 0.2 microM and 20 microM) but TNP-ATP (0.1-10 microM) inhibited EJPs by <30%. Noradrenaline (0.3-30 microM in the presence of phentolamine and propranolol) decreased EJPs in control preparations but facilitated EJPs by 5-20% in submucosal arterioles from reserpinized guinea-pigs. These properties are discussed in relation to P2X receptors underlying EJPs at autonomic neuroeffector junctions.

Animals↗

Multiple mechanisms of fast excitatory synaptic transmission in the enteric nervous system.

The enteric nervous system (ENS) can control gastrointestinal function independent of direct connections with the central nervous system. Enteric nerves perform this important function using multiple mechanisms of excitatory neurotransmission in enteric ganglia. Fast excitatory synaptic transmission in the autonomic nervous system (ANS) is largely mediated by acetylcholine (ACh) acting at nicotinic cholinergic receptors but in the ENS there are noncholinergic fast excitatory neurotransmitters. There are two broad types of neurons in the ENS: S neurons and AH neurons. S neurons are interneurons and motoneurons while AH neurons are sensory neurons. Three subsets of S neurons in the myenteric plexus can be distinguished on the basis of the neurotransmitters producing fast excitatory postsynaptic potentials (fEPSPs) in each subset. In one subset, fEPSPs are mediated solely by ACh acting at nicotinic cholinergic receptors. In a second subset of S neurons, ATP acting at P2X purine receptors and ACh contribute to the fEPSP while in a third subset, fEPSPs are mediated by 5-hydroxytryptamine (5-HT) acting at 5-HT(3) receptors and ACh. Some AH neurons also receive fast excitatory synaptic input. The fEPSPs recorded from AH neurons are mediated ACh and also by glutamate acting at alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. Multiple mechanisms of fast excitatory synaptic transmission in the ENS are likely to contribute to its capacity to regulate complex gastrointestinal functions.

Animals↗

Maximal accumulated oxygen deficit expressed relative to the active muscle mass for cycling in untrained male and female subjects.

The purpose of the present study was to determine if gender differences exist in the maximal accumulated oxygen deficit (MAOD) or in the blood lactate (Lac-) and catecholamine responses to the MAOD test (120% peak oxygen uptake to exhaustion). The MAOD for cycling was measured in ten untrained male and ten untrained female subjects using the method described by Medbø et al. (Anaerobic capacity determined by maximal accumulated oxygen deficit. J Appl Physiol 64: 50-60, 1988). Blood Lac- and catecholamine concentrations were measured at rest, exhaustion and for 30 min following the MAOD test. Dual-energy X-ray absorptiometry was used to measure lean body mass (LBM) and to estimate the active muscle mass (AMM) for cycling. Males achieved a significantly higher MAOD than females following correction for AMM [126.3 (5.6) versus 108.3 (6.1) ml x kg AMM(-1), P = 0.04]. The peak blood lactate concentration ([Lac-]) in males [13.6 (0.9) mmol x l(-1)] was significantly higher than in females [10.0 (1.0) mmol x l(-1)]. Males obtained a 68% higher peak epinephrine concentration ([Epi]) than females, but the difference was not significant [1268 (188) pg x ml(-1) versus 755 (179) pg x ml(-1), P = 0.066]. However, plasma [Epi] was significantly higher for males than females at 1 min [824 (116) versus 489 (116) pg x ml(-1), P = 0.036] and 3 min [330 (52) versus 179 (42) pg x ml(-1), P = 0.039] into the recovery period. No gender-dependent differences in the norepinephrine concentration were observed at any time. Peak [Lac-] was significantly correlated with MAOD (ml x kg AMM(-1)) in females (r = 0.75), but not in males (r = 0.09). The peak plasma [Epi] was not significantly correlated with MAOD (ml x kg AMM(-1)) or peak [Lac-] in either group. These findings suggest that there are gender-dependent differences in MAOD even when expressed relative to the AMM for cycling. The higher blood [Lac-] in males compared to females obtained after supramaximal exercise was not caused by enhanced secretion of Epi. The greater MAOD in untrained males was not caused by a greater ability to produce Lac- or by enhanced secretion of Epi.

Absorptiometry, Photon↗

Plasma catecholamine and blood lactate responses to incremental arm and leg exercise.

PURPOSE AND METHODS: The present study was conducted to examine the pattern of plasma catecholamine and blood lactate responses to incremental arm and leg exercise. Seven untrained male subjects performed two incremental exercise tests on separate days in random order. One test consisted of 1-arm cranking (5W x 2 min(-1)), whereas the other exercise test was 2-leg cycling (20-25W x 2 min(-1)). Blood samples were obtained from the nonexercising arm during 1-arm cranking and from the same arm and vein during 2-leg cycling. Thresholds for blood lactate (T(La)), epinephrine (T(Epi)) and norepinephrine (T(NE)) were determined for each subject under both exercise conditions and defined as breakpoints when plotted as a function of power output. RESULTS: When the two modes of exercise were compared, T(La), T(Epi), and T(NE) were all significantly lower for 1-arm cranking than for 2-leg cycling (P < 0.01). During 1-arm cranking, T(La) (0.96 +/- 0.10 L x min(-1)), T(Epi) (1.02 +/- 0.07 L x min(-1)), and T(NE) (1.07 +/- 0.09 L x min(-1)) occurred simultaneously. During 2-leg cycling, T(La) (1.77 +/- 0.20 L x min(-1)), T(Epi) (1.74 +/- 0.17 L x min(-1)), and T(NE) (1.98 +/- 0.17 L x min(-1)) occurred at similar levels of VO2 and were not significantly different. The correlation observed between the VO2 measured at the T(La) and T(Epi) was 0.917 for arm and 0.929 for leg exercise (P < 0.001). The epinephrine concentration ([Epi]) obtained at the T(La) was not significantly different for arm (0.144 ng x mL(-1)) and leg (0.152 ng x mL(-1)) exercise. CONCLUSIONS: The breakpoint in plasma [Epi] shifted in an identical manner and occurred simultaneously with that of T(La) regardless of the mode of exercise (arm or leg). The Epi concentrations observed at the T(La) agree with those previously reported to produce a rise in blood lactate during Epi infusion at rest. These results support the hypothesis that a rise in plasma [Epi] may contribute to the breakpoint in blood lactate that occurs during incremental exercise.

Adult↗

Presynaptic nicotinic acetylcholine receptors in the myenteric plexus of guinea pig intestine.

Presynaptic nicotinic acetylcholine receptors (nAChRs) were studied in myenteric plexus preparations from guinea pig ileum using intracellular electrophysiological methods. Microapplication of nicotine (1 mM) caused a biphasic depolarization in all AH neurons (n = 30) and in 36 of 49 S neurons. Cytisine (1 mM) caused fast depolarizations in S neurons and no response in AH neurons. Mecamylamine (10 microM) blocked all responses caused by nicotine and cytisine. TTX (0.3 microM) blocked slow excitatory synaptic potentials in S and AH neurons but had no effect on fast depolarizations caused by nicotine. Nicotine-induced slow depolarizations were reduced by TTX in two of twelve AH neurons (79% inhibition) and four of nine S neurons (90+/-12% inhibition). Slow nicotine-induced depolarizations in the remaining neurons were TTX resistant. TTX-resistant slow depolarizations were inhibited after neurokinin receptor 3 desensitization caused by senktide (0.1 microM); senktide desensitization inhibited the slow nicotine-induced depolarization by 81+/-5% and 63+/-15% in AH and S neurons, respectively. A low-calcium and high-magnesium solution blocked nicotine-induced slow depolarizations in AH neurons. In conclusion, presynaptic nAChRs mediate the release of substance P and/or neurokinin A to cause slow depolarizations of myenteric neurons.

Alkaloids↗

Use of dental care by HIV-infected medical patients.

Although increasing attention has been paid to the use of dental care by HIV patients, the existing studies do not use probability samples, and no accurate population estimates of use can be made from this work. The intent of the present study was to establish accurate population estimates of the use of dental services by patients under medical care. The study, part of the HIV Cost and Services Utilization Study (HCSUS), created a representative national probability sample, the first of its kind, of HIV-infected adults in medical care. Both bivariate and logistic regressions were conducted, with use of dental care in the preceding 6 months as the dependent variable and demographic, social, behavioral, and disease characteristics as independent variables. Forty-two percent of the sample had seen a dental health professional in the preceding 6 months. The bivariate logits for use of dental care show that African-Americans, those whose exposure to HIV was caused by hemophilia or blood transfusions, persons with less education, and those who were employed were less likely to use dental care (p < 0.05). Sixty-five percent of those with a usual source of care had used dental care in the preceding 6 months. Use was greatest among those obtaining dental care from an AIDS clinic (74%) and lowest among those without a usual source of dental care (12%). We conclude that, in spite of the high rate of oral disease in persons with HIV, many do not use dental care regularly, and that use varies by patient characteristics and availability of a regular source of dental care.

Adolescent↗

Perceived unmet need for oral treatment among a national population of HIV-positive medical patients: social and clinical correlates.

OBJECTIVES: This study examines social, behavioral, and clinical correlates of perceived unmet need for oral health care for people with HIV infection. METHODS: Baseline in-person interviews with 2864 individuals were conducted with the HIV Cost and Services Utilization Study cohort, a nationally representative probability sample of HIV-infected persons in medical care. Bivariate and logistic regression analyses were conducted, with unmet need in the last 6 months as the dependent variable and demographic, social, behavioral, and disease characteristics as independent variables. RESULTS: We estimate that 19.3% of HIV-infected medical patients (n = 44,550) had a perceived unmet need for dental care in the last 6 months. The odds of having unmet dental needs were highest for those on Medicaid in states without dental benefits (odds ratio [OR] = 2.21), for others with no dental insurance (OR = 2.26), for those with incomes under $5000 (OR = 2.20), and for those with less than a high school education (OR = 1.83). Low CD4 count was not significant. CONCLUSIONS: Perceived unmet need was related more to social and economic factors than to stage of infection. An expansion of dental benefits for those on Medicaid might reduce unmet need for dental care.

Adult↗

Tracheobronchial mucus viscoelasticity during environmental challenge in horses with recurrent airway obstruction.

The goal of this study was to compare the rheological properties of mucus from horses with recurrent airway obstruction (RAO) to that from healthy controls during environmental challenge by stabling in stalls with straw as bedding and hay as feed. We determined viscoelasticity (log G* dyn/cm2, at 10 radian/s) and calculated mucociliary clearability index (MCI) and cough clearability index (CCI), which are derivative parameters of G* and the ratio of viscosity and elasticity measured at 1 and 100 radian/s, respectively. We also investigated the solids content of mucus, and cytology of bronchoalveolar lavage fluid (BALF). Samples were obtained before (0 h) and 6, 24 and 48 h after environmental challenge. The central findings were rheological changes in airway mucus, which occurred over time in RAO-affected animals, but not in controls. Mucus rheology was similar in both groups at 0 and 6 h. In RAO-affected horses, mucus viscoelasticity, as measured by log G*, increased from 2.49 +/- 0.18 dyn/cm2 (mean +/- s.e.) at 0 h to 3.05 +/- 0.13 dyn/cm2 at 24 h after environmental challenge, and was accompanied by significant decreases in MCI and CCI. Percent solids of mucus did not differ significantly between the 2 groups, nor over time. Rheological values did not correlate with BALF cytology. We conclude that viscoelastic properties of tracheal mucus samples from RAO horses in remission do not differ from those of normal horses. However, environmental challenge causes clinical signs of small airway disease and a concurrent increase in mucus viscoelasticity only in RAO horses. Therefore, we infer that unfavourable changes in mucus rheology may contribute to stasis and accumulation of mucus in RAO horses in exacerbation, but not in clinical remission.

Airway Obstruction↗

Nicotinic acetylcholine receptors at sites of neurotransmitter release to the guinea pig intestinal circular muscle.

Experiments were designed to test the hypothesis that nicotinic acetylcholine receptors (nAChRs) are present at sites of neurotransmission to the guinea pig ileum circular smooth muscle. Circular smooth muscle preparations, from which the myenteric plexus had been removed (circular muscle-axon preparation), were used for this purpose. Nicotine and dimethylphenyl piperazinium iodide (10-100 microM) induced contraction of the circular smooth muscle. Agonist-induced contraction was inhibited by 1 microM scopolamine and abolished in the combined presence of 1 microM scopolamine and 0. 3 microM CP 96,345-01, a neurokinin-1 receptor antagonist. Contractions induced by electric field stimulation (30 pulses, 0.5 ms, 70 V, 10 Hz) were abolished by 0.3 microM tetrodotoxin (TTX); in contrast, agonist-induced contraction was attenuated but not abolished by 0.3 microM TTX. Mecamylamine (3 or 30 microM), an nAChR antagonist, blocked agonist-induced contractions. Frequency-response curves for both "ON and "OFF electric field stimulation contractions were abolished by the combined presence of 1 microM scopolamine and 0.3 microM CP 96,345-01 or by 0.3 microM TTX. At stimulation frequencies greater than 2 Hz, the ON contraction was increased in the presence of 100 microM nitro-L-arginine. Mecamylamine (3 microM) was used to block the stimulatory prejunctional nAChRs located near sites of neurotransmitter release to the circular smooth muscle; however, ON and OFF contractions were not affected by mecamylamine. Although the prejunctional nAChRs are not targets for endogenously released acetylcholine under the conditions tested here, these receptors may be targets for the development of new prokinetic agents.

Animals↗

VO2peak and the gas-exchange anaerobic threshold during incremental arm cranking in able-bodied and paraplegic men.

Resting energy expenditure, peak oxygen uptake (VO2peak) and the gas-exchange anaerobic threshold (Than) were measured during incremental arm cranking (15 W x min(-1)) in six able-bodied (AB) and six paraplegic (P) subjects. Only male subjects with traumatic spinal cord injuries in the area of the 10-12th thoracic segment were included in the P group. All AB and P subjects were physically active. Mean (SE) values for age and body mass were 28 (2) years and 78.9 (3.9) kg for the AB group and 32 (4) years and 70.8 (7.9) kg for the P group (P>0.05). Resting energy expenditure values were not found to be significantly different between AB [5.8 (0.2) kJ x min(-1)] and P [5.1 (0.3) kJ min(-1)] subjects. Mean VO2peak values were 29.3 (2.4) ml x kg(-1) min(-1) and 29.6 (2.2) ml x kg(-1) x min(-1) for the AB and P groups, respectively (P>0.05). Absolute oxygen uptake values measured at two gas-exchange anaerobic threshold (Than) were not significantly different between the two groups. However, the Than occurred at a significantly higher percentage of VO2peak in the P [58.9 (1.7)%] group than in the AB [50.0 (2.8)%] group (P<0.05). Moreover, respiratory exchange ratio (R) values obtained at the Than and at 15, 45, 60, 75 and 90 W of incremental exercise were significantly lower in the P group than in the AB group. Heart rates were significantly elevated at every submaximal work stage (15-120 W) in the P group compared to the AB group (P<0.05). These findings suggest that chronic daily wheelchair activity produces local adaptations in the functional upper-body musculature, which reduce glycogenolysis and increase the rate of lipid utilization (lower R) during arm exercise. These local adaptations may be in part responsible for the significantly higher Than observed for arm exercise in P subjects, even though VO2peak values were essentially the same for both groups.

Adult↗