bluuebunny/crossref_metadata_2025 huggingface dataset:
Anandamide content and interaction of endocannabinoid/GABA modulatory effects in the NTS on baroreflex-evoked sympathoinhibition
Authors: Seagard Jeanne L. , Dean Caron , Patel Sachin , Rademacher David J. , Hopp Francis A. , Schmeling William T. , Hillard Cecilia J.
Published: February 2004

Cannabinoids have been shown to modulate central autonomic regulation and baroreflex control of blood pressure (BP). The presence of cannabinoid CB1 receptors on fibers in the nucleus tractus solitarius (NTS) suggests that some presynaptic modulation of transmitter release could occur in this region, which receives direct afferent projections from arterial baroreceptors and cardiac mechanoreceptors. This study, therefore, was performed to determine the mechanism(s) of effects of microinjection of an endocannabinoid, arachidonylethanolamide (anandamide, AEA), into the NTS on baroreflex sympathetic nerve responses produced by phenylephrine-induced pressure changes in anesthetized rats. AEA prolonged reflex inhibition of renal sympathetic nerve activity (RSNA), suggesting an increase in baroreflex sensitivity. This effect of AEA was blocked by prior microinjection of SR-141716 to block cannabinoid CB1 receptors. To determine whether this baroreflex enhancement by AEA involved a GABAA mechanism, the baroreflex response to AEA was tested after prior blockade of postsynaptic GABAA receptors by bicuculline, which would eliminate any effects due to modulation of GABA activity. After bicuculline, which alone prolonged the baroreflex inhibition of RSNA, AEA shortened the duration of RSNA inhibition, suggesting a possible presynaptic inhibition of glutamate release previously obscured by a more dominant GABAA effect. To support a possible physiological role for AEA, AEA concentration in the NTS was measured after a phenylephrine-induced increase in BP. AEA content in the NTS was increased significantly over that in normotensive animals. These results support the hypothesis that AEA content is increased by brief periods of hypertension and suggest that AEA can modulate the baroreflex through activation of CB1 receptors within the NTS, possibly modulating effectiveness of GABA and/or glutamate neurotransmission.
Vasodilator effect and mechanism of action of vascular endothelial growth factor in skin vasculature
Authors: Ashrafpour Homa , Huang Ning , Neligan Peter C. , Forrest Christopher R. , Addison Patrick D. , Moses Michael A. , Levine Ronald H. , Pang Cho Y.
Published: February 2004

Various laboratories have reported that local subcutaneous or subdermal injection of VEGF165 at the time of surgery effectively attenuated ischemic necrosis in rat skin flaps, but the mechanism was not studied and enhanced angiogenesis was implicated. In the present study, we used the clinically relevant isolated perfused 6 × 16-cm pig buttock skin flap model to 1) test our hypothesis that VEGF165 is a potent vasodilator and acute VEGF165 treatment increases skin perfusion; and 2) investigate the mechanism of VEGF165-induced skin vasorelaxation. We observed that VEGF165 (5 × 10–16–5 × 10–11 M) elicited a concentration-dependent decrease in perfusion pressure (i.e., vasorelaxation) in skin flaps preconstricted with a submaximal concentration of norepinephrine (NE), endothelin-1, or U-46619. The VEGF165-induced skin vasorelaxation was confirmed using a dermofluorometry technique for assessment of skin perfusion. The vasorelaxation potency of VEGF165 in NE-preconstricted skin flaps (pD2 = 13.57 ± 0.31) was higher ( P < 0.05) than that of acetylcholine (pD2 = 7.08 ± 0.24). Human placental factor, a specific VEGF receptor-1 agonist, did not elicit any vasorelaxation effect. However, a specific antibody to VEGF receptor-2 (1 μg/ml) or a specific VEGF receptor-2 inhibitor (5 × 10–6 M SU-1498) blocked the vasorelaxation effect of VEGF165 in NE-preconstricted skin flaps. These observations indicate that the potent vasorelaxation effect of VEGF165 in the skin vasculature is initiated by the activation of VEGF receptor-2. Furthermore, using pharmacological probes, we observed that the postreceptor signaling pathways of VEGF165-induced skin vasorelaxation involved activation of phospholipase C and protein kinase C, an increase in inositol 1,4,5-trisphosphate activity, release of the intra-cellular Ca2+ store, and synthesis/release of endothelial nitric oxide, which predominantly triggered the effector mechanism of VEGF165-induced vasorelaxation. This information provides, for the first time, an important insight into the mechanism of VEGF165 protein or gene therapy in the prevention/treatment of ischemia in skin flap surgery and skin ischemic diseases.
Pyrimidine nucleotides suppress KDRcurrents and depolarize rat cerebral arteries by activating Rho kinase
Authors: Luykenaar Kevin D. , Brett Suzanne E. , Wu Bin Nan , Wiehler William B. , Welsh Donald G.
Published: February 2004

This study examined whether, and by what signaling and ionic mechanisms, pyrimidine nucleotides constrict rat cerebral arteries. Cannulated cerebral arteries stripped of endothelium and pressurized to 15 mmHg constricted in a dose-dependent manner to UTP. This constriction was partly dependent on the depolarization of smooth muscle cells and the activation of voltage-operated Ca2+channels. The depolarization and constriction induced by UTP were unaffected by bisindolylmaleimide I, a PKC inhibitor that abolished phorbol ester (PMA)-induced constriction in cerebral arteries. In contrast, the Rhokinase inhibitor Y-27632 attenuated the ability of UTP to both constrict and depolarize cerebral arteries. With patch-clamp electrophysiology, a voltage-dependent delayed rectifying K+(KDR) current was isolated and shown to consist of a slowly inactivating 4-aminopyridine (4-AP)-sensitive and an -insensitive component. The 4-AP-sensitive KDRcurrent was potently suppressed by UTP through a mechanism that was not dependent on PKC. This reflects observations that demonstrated that 1) a PKC activator (PMA) had no effect on KDRand 2) PKC inhibitors (calphostin C or bisindolylmaleimide I) could not prevent the suppression of KDRby UTP. The Rho kinase inhibitor Y-27632 abolished the ability of UTP to inhibit the KDRcurrent, as did inhibition of RhoA with C3 exoenzyme. Cumulatively, these observations indicate that Rho kinase signaling plays an important role in eliciting the cerebral constriction induced by pyrimidine nucleotides. Moreover, they demonstrate for the first time that Rhokinase partly mediates this constriction by altering ion channels that control membrane potential and Ca2+influx through voltage-operated Ca2+channels.
Pressure overload-induced LV hypertrophy and dysfunction in mice are exacerbated by congenital NOS3 deficiency
Authors: Ichinose Fumito , Bloch Kenneth D. , Wu Justina C. , Hataishi Ryuji , Aretz H. Thomas , Picard Michael H. , Scherrer-Crosbie Marielle
Published: February 2004

To investigate the role of endothelial nitric oxide synthase (NOS3) in left ventricular (LV) remodeling induced by chronic pressure overload, the impact of transverse aortic constriction (TAC) on LV structure and function was compared in wild-type (WT) and NOS3-deficient (NOS3–/–) mice. Before TAC, LV wall thickness, mass, and fractional shortening were similar in the two mouse strains. Twenty-eight days after TAC, both WT and NOS3–/– mice had increased LV wall thickness and mass as well as decreased fractional shortening. Although the pressure gradient across the TAC was similar in both strains of mice 28 days after TAC, LV mass and posterior wall thickness were greater in NOS3–/– than in WT mice, whereas fractional shortening and the maximum rate of developed LV pressure were less. Diastolic function, as measured by the time constant of isovolumic relaxation and the maximum rate of LV pressure decay, was impaired to a greater extent in NOS3–/– than in WT mice. The degree of myocyte hypertrophy and LV fibrosis was greater in NOS3–/– than in WT mice at 28 days after TAC. Mortality was greater in NOS3–/– than in WT mice 28 days after TAC. Long-term administration of hydralazine normalized the blood pressure and prevented the LV dilation in NOS3–/– mice but did not prevent the LV hypertrophy, dysfunction, and fibrosis associated with NOS3 deficiency after TAC. These results suggest that the absence of NOS3 augments LV dysfunction and remodeling in a murine model of chronic pressure overload.
Physiological evaluation of a new quantitative SPECT method measuring regional ventilation and perfusion
Authors: Petersson Johan , Sánchez-Crespo Alejandro , Rohdin Malin , Montmerle Stéphanie , Nyrén Sven , Jacobsson Hans , Larsson Stig A. , Lindahl Sten G. E. , Linnarsson Dag , Glenny Robb W. , Mure Margareta
Published: February 2004

We have developed a new quantitative single-photon-emission computed tomography (SPECT) method that uses113mIn-labeled albumin macroaggregates and Technegas (99mTc) to estimate the distributions of regional ventilation and perfusion for the whole lung. The multiple inert-gas elimination technique (MIGET) and whole lung respiratory gas exchange were used as physiological evaluations of the SPECT method. Regional ventilation and perfusion were estimated by SPECT in nine healthy volunteers during awake, spontaneous breathing. Radiotracers were administered with subjects sitting upright, and SPECT images were acquired with subjects supine. Whole lung gas exchange of MIGET gases and arterial Po2and Pco2gases was predicted from estimates of regional ventilation and perfusion. We found a good agreement between measured and SPECT-predicted exchange of MIGET and respiratory gases. Correlations ( r2) between SPECT-predicted and measured inert-gas excretions and retentions were 0.99. The method offers a new tool for measuring regional ventilation and perfusion in humans.
Attenuation of baroreflex sensitivity after domoic acid lesion of the nucleus ambiguus of rats
Authors: Cheng Zixi (Jack) , Zhang Hong , Yu Jerry , Wurster Robert D. , Gozal David
Published: February 2004

The nucleus ambiguus (NA) and the dorsal motor nucleus of the vagus (DmnX) innervate distinct populations of cardiac ganglionic principal neurons. This anatomic evidence suggests that these two nuclei play different roles (Cheng Z and Powley TL, Soc Neurosci Abstr 26: 1189, 2000). However, lesion of the DmnX does not attenuate baroreflex sensitivity (Cheng Z, Guo SZ, Lipton AJ, and Gozal D, J Neurosci 22: 3215–3226, 2002). The present study tested the functional role of the NA in baroreflex control of heart rate (HR). Domoic acid (DA) was injected into the left NA of Sprague-Dawley rats to lesion the NA. The neuronal loss was assessed using retrograde labeling and confocal microscopy. HR changes induced by phenylephrine and sodium nitroprusside administration and after electrical stimulation of the left vagal trunk were measured at 15 days, and HR responses to left NA microinjection of l-glutamate were determined at 180 days postlesion. Compared with vehicle injections, DA lesions significantly reduced the population of NA motor neurons by ∼68% ( P < 0.01) and attenuated baroreflex sensitivity by ∼83% ( P < 0.01) at 15 days. Similarly, electrical stimulation of the vagal trunk of DA-lesioned animals led to attenuated decreases in HR responses. NA neuronal counts were reduced by ∼81% ( P < 0.01) and mean HR responses to l-glutamate injection into the lesioned NA were attenuated by ∼65% ( P < 0.01) at 180 days. Therefore, the NA plays a major role in baroreflex control of HR, and the integrity of the NA is critically important for the normal baroreflex control. In addition, NA lesions produce long-term anatomic and functional dysfunction of the nucleus, and thus it may provide an useful model for functional assessment of respective roles of the NA and DmnX.
Recovery of microvascular Po2during the exercise off-transient in muscles of different fiber type
Authors: McDonough Paul , Behnke Brad J. , Musch Timothy I. , Poole David C.
Published: February 2004

The speed with which muscle energetic status recovers after exercise is dependent on oxidative capacity and vascular O2pressures. Because vascular control differs between muscles composed of fast- vs. slow-twitch fibers, we explored the possibility that microvascular O2pressure (PmvO2; proportional to the O2delivery-to-O2uptake ratio) would differ during recovery in fast-twitch peroneal (Per: 86% type II) compared with slow-twitch soleus (Sol: 84% type I). Specifically, we hypothesized that, in Per, PmvO2would be reduced immediately after contractions and would recover more slowly during the off-transient from contractions compared with Sol. The Per and Sol muscles of six female Sprague-Dawley rats (weight = ∼220 g) were studied after the cessation of electrical stimulation (120 s; 1 Hz) to compare the recovery profiles of PmvO2. As hypothesized, PmvO2was lower throughout recovery in Per compared with Sol (end contraction: 13.4 ± 2.2 vs. 20.2 ± 0.9 Torr; end recovery: 24.0 ± 2.4 vs. 27.4 ± 1.2 Torr, Per vs. Sol; P ≤ 0.05). In addition, the mean response time for recovery was significantly faster for Sol compared with Per (45.1 ± 5.3 vs. 66.3 ± 8.1 s, Sol vs. Per; P < 0.05). Despite these findings, PmvO2rose progressively in both muscles and at no time fell below end-exercise values. These data indicate that, during the recovery from contractions (which is prolonged in Per), capillary O2driving pressure (i.e., PmvO2) is reduced in fast-compared with slow-twitch muscle. In conclusion, the results of the present investigation may partially explain the slowed recovery kinetics (phosphocreatine and O2uptake) found previously in 1) fast- vs. slow-twitch muscle and 2) various patient populations, such as those with congestive heart failure and diabetes mellitus.
Peripheral chemoreflex responsiveness is increased at elevated levels of carbon dioxide after episodic hypoxia in awake humans
Authors: Mateika Jason H. , Mendello Chris , Obeid Dany , Badr M. Safwan
Published: February 2004

We hypothesized that the acute ventilatory response to hypoxia is enhanced after exposure to episodic hypoxia in awake humans. Eleven subjects completed a series of rebreathing trials before and after exposure to eight 4-min episodes of hypoxia. During the rebreathing trials, subjects initially hyperventilated to reduce the partial pressure of carbon dioxide (PetCO2) below 25 Torr. Subjects then breathed from a bag containing normocapnic (42 Torr), low (50 Torr), or high oxygen (140 Torr) gas mixtures. During the trials, PetCO2 increased while a constant oxygen level was maintained. The point at which ventilation began to rise in a linear fashion as PetCO2 increased was considered to be the ventilatory recruitment threshold. The ventilatory response below and above the recruitment threshold was determined. Ventilation did not persist above baseline values immediately after exposure to episodic hypoxia; however, PetCO2 levels were reduced compared with baseline. In contrast, compared with baseline, the ventilatory response to progressive increases in carbon dioxide during rebreathing trials in the presence of low but not high oxygen levels was increased after exposure to episodic hypoxia. This increase occurred when carbon dioxide levels were above but not below the ventilatory recruitment threshold. We conclude that long-term facilitation of ventilation (i.e., increases in ventilation that persist when normoxia is restored after episodic hypoxia) is not expressed in awake humans in the presence of hypocapnia. Nevertheless, despite this lack of expression, the acute ventilatory response to hypoxia in the presence of hypercapnia is increased after exposure to episodic hypoxia.
Venous occlusion to the lower limb attenuates vasoconstriction in the nonexercised limb during posthandgrip muscle ischemia
Authors: Tokizawa K. , Mizuno M. , Nakamura Y. , Muraoka I.
Published: February 2004

We investigated the effects of increases in calf volume on cardiovascular responses during handgrip (HG) exercise and post-HG exercise muscle ischemia (PEMI). Seven subjects completed two trials: one control (no occlusion) and one venous occlusion (VO) session. Both trials included a baseline measurement followed by 15 min of rest (REST), 2 min of HG, and 2 min of PEMI. VO was applied at 100 mmHg via cuffs placed around both distal thighs during REST, HG, and PEMI. Mean arterial pressure, heart rate, forearm blood flow (FBF) in the nonexercised arm, and forearm vascular resistance (FVR) in the nonexercised arm (FVR) were measured. During REST and HG, there were no significant differences between trials in all parameters. During PEMI in the control trial, mean arterial pressure and FVR were significantly greater and FBF was significantly lower than baseline values ( P < 0.05 for each). In contrast, in the VO trial, FBF and FVR responses were different from control responses. In the VO trial, FBF was significantly greater than in the control trial (4.7 ± 0.5 vs. 2.5 ± 0.3 ml·100 ml-1·min-1, P < 0.05) and FVR was significantly lower (28.0 ± 4.8 vs. 49.1 ± 4.6 units, respectively, P < 0.05). These results indicate that increases in vascular resistance in the nonexercised limb induced by activation of the muscle chemoreflex can be attenuated by increases in calf volume.
Retinoic acid induces nonuniform alveolar septal growth after right pneumonectomy
Authors: Yan Xiao , Bellotto Dennis J. , Foster David J. , Johnson Robert L. , Hagler Herbert K. , Estrera Aaron S. , Hsia Connie C. W.
Published: February 2004

To determine whether all- trans retinoic acid (RA) enhances compensatory lung growth in fully mature animals, adult male dogs ( n = 4) received 2 mg·kg-1·day-1 po RA 4 days/wk beginning the day after right pneumonectomy (R-PNX, 55-58% resection). Litter-matched male R-PNX controls ( n = 4) received placebo. After 4 mo, the remaining lung was fixed by tracheal instillation of fixatives at a constant airway pressure for detailed morphometric analysis. After RA treatment compared with placebo, lung volume was slightly but not significantly lower. Volume density of septum to lung was 37% higher because of a 50 and 25% higher volume density of capillary and septal tissue, respectively. Mean septal thickness was 27% higher. Absolute volumes of endothelial cells and capillary blood were 31-37% higher, whereas epithelial and interstitial volumes were not different between groups. Absolute alveolar-capillary surface areas did not differ between groups, and alveolar septal surface-to-volume ratio was 20% lower in RA-treated animals. RA treatment exaggerated interlobar differences in morphometric indexes and caused alveolar capillary morphology to revert to a more immature state. Thus RA treatment during early post-R-PNX adaptation preferentially enhanced alveolar capillary and endothelial cell volumes consistent with formation of new capillaries, but the associated septal distortion precluded a corresponding increase in gas-exchange surface or morphometric estimates of lung diffusing capacity.
Postexercise protein supplementation improves health and muscle soreness during basic military training in marine recruits
Authors: Flakoll Paul J. , Judy Tom , Flinn Kim , Carr Christopher , Flinn Scott
Published: February 2004

Elevated postexercise amino acid availability has been demonstrated to enhance muscle protein synthesis acutely, but the long-term impact of postexercise protein supplementation on variables such as health, muscle soreness, and function are unclear. Healthy male US Marine recruits from six platoons (US Marine Corps Base, Parris Island, SC; n = 387; 18.9 ± 0.1 yr, 74.7 ± 1.1 kg, 13.8 ± 0.4% body fat) were randomly assigned to three treatments within each platoon. Nutrients supplemented immediately postexercise during the 54-day basic training were either placebo (0 g carbohydrate, 0 g protein, 0 g fat), control (8, 0, 3), or protein supplement (8, 10, 3). Subjects and observers making measurements and data analysis were blinded to subject groupings. Compared with placebo and control groups, the protein-supplemented group had an average of 33% fewer total medical visits, 28% fewer visits due to bacterial/viral infections, 37% fewer visits due to muscle/joint problems, and 83% fewer visits due to heat exhaustion. Recruits experiencing heat exhaustion had greater body mass, lean, fat, and water losses. Muscle soreness immediately postexercise was reduced by protein supplementation vs. placebo and control groups on both days 34 and 54. Postexercise protein supplementation may not only enhance muscle protein deposition but it also has significant potential to positively impact health, muscle soreness, and tissue hydration during prolonged intense exercise training, suggesting a potential therapeutic approach for the prevention of health problems in severely stressed exercising populations.
Retinoic acid-induced alveolar cellular growth does not improve function after right pneumonectomy
Authors: Dane D. Merrill , Yan Xiao , Tamhane Rahul M. , Johnson Robert L. , Estrera Aaron S. , Hogg Deborah C. , Hogg Richard T. , Hsia Connie C. W.
Published: February 2004

To determine whether all- trans retinoic acid (RA) treatment enhances lung function during compensatory lung growth in fully mature animals, adult male dogs ( n = 4) received 2 mg·kg-1·day-1po RA 4 days/wk beginning the day after right pneumonectomy (R-PNX, 55-58% resection). Litter-matched male R-PNX controls ( n = 4) received placebo. After 3 mo, transpulmonary pressure (TPP)-lung volume relationship, diffusing capacities for carbon monoxide and nitric oxide, cardiac output, and septal volume (Vtiss-RB) were measured under anesthesia by a rebreathing technique at two lung volumes. Lung air and tissue volumes (Vair-CTand Vtiss-CT) were also measured from high-resolution computerized tomographic (CT) scans at a constant TPP. In RA-treated dogs compared with controls, TPP-lung volume relationships were similar. Diffusing capacities for carbon monoxide and nitric oxide were significantly impaired at a lower lung volume but similar at a high lung volume. Whereas Vtiss-RBwas significantly lower at both lung volumes in RA-treated animals, Vair-CTand Vtiss-CTwere not different between groups; results suggest uneven distribution of ventilation consistent with distortion of alveolar geometry and/or altered small airway function induced by RA. We conclude that RA does not improve resting pulmonary function during the early months after R-PNX despite histological evidence of its action in enhancing alveolar cellular growth in the remaining lung.
Parabrachial neurons mediate dorsal periaqueductal gray evoked respiratory responses in the rat
Authors: Hayward Linda F. , Castellanos Mabelin , Davenport Paul W.
Published: February 2004

The neural substrates mediating autonomic components of the behavioral defense response reside in the periaqueductal gray (PAG). The cardiovascular components of the defense response evoked from the dorsal PAG (DPAG) have been well described and are dependent, in part, on the integrity of neurons in the region of the parabrachial nucleus as well as the rostral ventrolateral medulla. Descending pathways mediating the ventilatory response associated with activation of DPAG neurons are unknown. The present study was undertaken to test the hypothesis that parabrachial area neurons are also involved in mediating the respiratory response to DPAG stimulation. In urethane-anesthetized, spontaneously breathing rats, electrical stimulation of the DPAG significantly increased respiratory rate, arterial pressure, and heart rate. Changes in respiratory frequency were associated with significant decreases in inspiratory and expiratory durations. After bilateral inhibition of neurons in the lateral parabrachial nucleus (LPBN) region with 5 mM muscimol ( n = 6), DPAG-evoked increases in respiration and heart rate were attenuated by 90 ± 6 and 72 ± 13%, respectively. The pressor response evoked by DPAG stimulation, however, was attenuated by only 57 ± 6%. Bilateral blockade of glutamate receptors with 20 mM kynurenic acid ( n = 6) in the LPBN also markedly attenuated DPAG-evoked increases in respiration and heart rate (65 ± 15 and 53 ± 9% reduction, respectively) but only modestly changed the DPAG-evoked pressor response (34 ± 16% reduction). These results demonstrate that LPBN neurons play a significant role in the DPAG-mediated respiratory component of behavioral defense responses. This finding supports previous work demonstrating that the dorsolateral pons plays a significant role in mediating most physiological adjustments associated with activation of the DPAG.
An age-related shift in the force-frequency relationship affects quadriceps fatigability in old adults
Authors: Allman Brian L. , Rice Charles L.
Published: February 2004

We examined the effect of an age-related leftward shift in the force-frequency relationship on the comparative quadriceps fatigability of nine young (27 ± 1 yr old) and nine old men (78 ± 1 yr old) during low-frequency electrical stimulation. Two different protocols of intermittent trains (6 pulses on, 650 ms off) of electrical stimulation at 25% maximum voluntary contraction were performed by both groups: 1) 180 trains at 14.3 Hz [constant frequency (CF) protocol], and 2) 180 trains at the frequency corresponding to 60% of each subject's force-frequency curve [normalized frequency (NF) protocol; young 14.9 ± 0.4 vs. old 12.7 ± 0.5 Hz; P < 0.05]. The quadriceps of the old men were weaker (∼31%) and relaxation was slower compared with the young men, as assessed by the maximal relaxation rate constant of the 50-Hz tetanus (young 12.1 ± 0.2 vs. old 9.2 ± 0.5 s-1; P < 0.05) and a leftward shift in the force-frequency relationship. The NF protocol revealed a decreased fatigability in the quadriceps with old age (percentage of 1st contraction force remaining at 180th: old 63.4 ± 1.5 vs. young 58.2 ± 1.7%; P < 0.05) that was masked during the CF protocol (old 60.7 ± 1.6 vs. young 58.6 ± 2.3%; P > 0.05). Irrespective of the protocol, the maximal relaxation rate was reduced to ∼73 and ∼57% of the prefatigue value in the young and old men, respectively. The age-related leftward shift in the force-frequency relationship of the quadriceps contributed to an underestimation of the fatigue resistance with old age during the CF protocol. However, when the stimulation frequency used in the NF protocol was adjusted to account for the age-related shift in the force-frequency relationship, the quadriceps muscles of the old men were less fatigable than those of the young men. Thus we suggest that whole muscle fatigability is better examined by electrical stimulation protocols that are adjusted for inter- and intragroup differences in the force-frequency relationship.
Effects of postural changes and vestibular lesions on genioglossal muscle activity in conscious cats
Authors: Cotter L. A. , Arendt H. E. , Cass S. P. , Jian B. J. , Mays D. F. , Olsheski C. J. , Wilkinson K. A. , Yates B. J.
Published: February 2004

Previous studies in humans showed that genioglossal muscle activity is higher when individuals are supine than when they are upright, and prior experiments in anesthetized or decerebrate animals suggested that vestibular inputs might participate in triggering these alterations in muscle firing. The present study determined the effects of whole body tilts in the pitch (nose-up) plane on genioglossal activity in a conscious feline model and compared these responses with those generated by roll (ear-down) tilts. We also ascertained the effects of a bilateral vestibular neurectomy on the alterations in genioglossal activity elicited by changes in body position. Both pitch and roll body tilts produced modifications in muscle firing that were dependent on the amplitude of the rotation; however, the relative effects of ear-down and nose-up tilts on genioglossal activity were variable from animal to animal. The response variability observed might reflect the fact that genioglossus has a complex organization and participates in a variety of tongue movements; in each animal, electromyographic recordings presumably sampled the firing of different proportions of fibers in the various compartments and subcompartments of the muscle. Furthermore, removal of labyrinthine inputs resulted in alterations in genioglossal responses to postural changes that persisted until recordings were discontinued ∼1 mo later, demonstrating that the vestibular system participates in regulating the muscle's activity. Peripheral vestibular lesions were subsequently demonstrated to be complete through the postmortem inspection of temporal bone sections or by observing that vestibular nucleus neurons did not respond to rotations in vertical planes.
Activation of thin-fiber muscle afferents by a P2X agonist in cats
Authors: Hanna Ramy L. , Kaufman Marc P.
Published: February 2004

The responses of group III and IV triceps surae muscle afferents to intra-arterial injection of α,β-methylene ATP (50 μg/kg) was examined in decerebrate cats. We found that this P2X3 agonist stimulated only three of 18 group III afferents but 7 of 9 group IV afferents ( P < 0.004). The three group III afferents stimulated by α,β-methylene ATP conducted impulses below 4 m/s. Pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid, a P2-receptor antagonist, prevented the stimulation of these afferents by α,β-methylene ATP. We conclude that P2X3 agonists stimulate only the slowest conducting group III muscle afferents as well as group IV afferents.
Cardiovascular and respiratory responses to apneas with and without face immersion in exercising humans
Authors: Andersson Johan P. A. , Linér Mats H. , Fredsted Anne , Schagatay Erika K. A.
Published: February 2004

The effect of the diving response on alveolar gas exchange was investigated in 15 subjects. During steady-state exercise (80 W) on a cycle ergometer, the subjects performed 40-s apneas in air and 40-s apneas with face immersion in cold (10°C) water. Heart rate decreased and blood pressure increased during apneas, and the responses were augmented by face immersion. Oxygen uptake from the lungs decreased during apnea in air (-22% compared with eupneic control) and was further reduced during apnea with face immersion (-25% compared with eupneic control). The plasma lactate concentration increased from control (11%) after apnea in air and even more after apnea with face immersion (20%), suggesting an increased anaerobic metabolism during apneas. The lung oxygen store was depleted more slowly during apnea with face immersion because of the augmented diving response, probably including a decrease in cardiac output. Venous oxygen stores were probably reduced by the cardiovascular responses. The turnover times of these gas stores would have been prolonged, reducing their effect on the oxygen uptake in the lungs. Thus the human diving response has an oxygen-conserving effect.
Intraluminal pressure oscillation enhances subsequent airway contraction in isolated bronchial segments
Authors: Noble P. B. , McFawn P. K. , Mitchell H. W.
Published: February 2004

A period of deep inspiration in humans has been shown to attenuate subsequent bronchoconstriction, a phenomenon termed bronchoprotection. The bronchoprotective effect of deep inspiration may be caused though a depression in the force production of airway smooth muscle (ASM). We determined the response of whole airway segments and isolated ASM to a period of cyclic stretches. Isovolumetric contraction to electrical field stimulation (EFS) was assessed in porcine bronchial segments before and after intraluminal pressure oscillation from 5 to 25 cmH2O for 10 min at 0.5 Hz. Morphometry showed that this pressure oscillation stretched ASM length by 21%. After pressure oscillation, the response to EFS was not reduced but instead was modestly enhanced ( P < 0.01). Airway responses to EFS returned to preoscillation levels 10 min after the end of oscillation. The increase in EFS response after pressure oscillation was not altered by the addition of indomethacin. In a separate experiment, we assessed isometric force in isolated ASM strips before and after length oscillation. The amplitude, frequency, and duration of length oscillation were similar to those induced in bronchial segments. In contrast to bronchial segments, length oscillation of ASM produced a significant depression in isometric force induced by EFS ( P < 0.01). These results suggest that the response of ASM to length oscillation is modified by the airway wall. They also suggest that the phenomenon of bronchoprotection reported in some in vivo studies may not be an intrinsic property of the airway.
Sources of Stem Cells: Ethical Controversies and Policy Developments in the United States
Authors: Childress James F.
Published: February 2004

The bioethical controversy about public policy in the United States regarding human stem cell research, particularly with regard to several potential sources of stem cells, including aborted fetuses, unimplanted embryos following in vitro fertilization (IVF), and embryos created through IVF or cloning for research purposes is examined. On the one hand, the debate about the use of federal funds for this research was not resolved by President Bush’s policy, announced in August 2001, because only a few cell lines are available under this restrictive policy. On the other hand, debate persists about whether the US should adopt a prohibitive, regulatory, or permissive policy toward the deliberate creation of embryos for biomedical research through somatic cell nuclear transfer. Although there is a wide consensus about the need to ban cloning-for-reproduction, there is deep division, reflected in the work of the President’s Council on Bioethics, about a possible ban on cloning-for-biomedical research. The author concludes that ethical controversy will probably persist about both types of policy, and that the policy stalemate will probably also continue, because of fundamental disagreements about the moral status of the early embryo.
Prenatal Diagnosis of Apert Syndrome
Authors: Hansen Wendy F. , Rijhsinghani Asha , Grant Stanley , Yankowitz Jerome
Published: February 2004

Objective: The role of the human fibroblast growth factor receptor (FGFR) gene family in current prenatal diagnosis and management of craniosynostosis syndromes and skeletal dysplasias is discussed. Method: We present the antenatal ultrasound findings, diagnosis, and management of 2 cases of Apert syndrome before and after molecular prenatal diagnosis was available. Results and Conclusion: Discovery of mutations in FGFR genes now allows the definitive antenatal diagnosis of Apert syndrome, other craniosynostosis syndromes, and skeletal dysplasias.
Congenital Visceral Malformations – Role of Perinatal Autopsy in Diagnosis
Authors: Mohan Harsh , Bhardwaj Shashi , Bal Amanjit
Published: February 2004

Objectives: Congenital malformations are one of the leading causes of perinatal deaths and infant mortality. The objective of the present study is to detect visceral malformations in perinatal autopsies. Design: A retrospective analysis of perinatal autopsies performed between 1998 and 2001 was done. Various visceral malformations were noted and categorized as urologic, cardiac, respiratory, gastrointestinal and miscellaneous. Results: Out of a total of 62 perinatal autopsies performed, congenital malformations were present in 38.7% of cases. Visceral malformations were observed in 24.1% of cases. Urologic malformations were the commonest (14.1%), followed by cardiac (8%) malformations. Associated external malformations were present in 6/15 cases, cardiac malformations being commonly associated with skeletal malformations. Conclusions: In all the cases, internal malformations were not suspected clinically. Thus, autopsy is an invaluable tool for detecting visceral malformations, adding to the clinical diagnosis and providing a feedback to the parents.
Characteristic Findings for Diagnosis of Baby Complicated with both the VACTERL Association and Duodenal Atresia
Authors: Fujishiro Emi , Suzuki Yoshikatsu , Sato Takeshi , Kondo Satoshi , Miyachi Masanao , Suzumori Kaoru
Published: February 2004

The VACTERL [vertebral defects (V), anal atresia (A), cardiac anomaly (C), tracheal-esophageal fistula with esophageal atresia (TE), renal defects (R), and radial limb dysplasia (L)] association can sometimes be diagnosed by ultrasonography and magnetic resonance imaging (MRI). Although the preaxial limb anomalies on ultrasonography were strongly associated with VACTERL association, the rate of limb anomalies is low. On ultrasonography, useful findings for prenatal diagnosis are a combination of esophageal atresia with hydramnion and renal anomalies. If esophageal atresia cannot be detected due to masking, diagnosis may be very difficult. In this case report, we reported the VACTERL association along with duodenal atresia. The detection of characteristic findings (enlarged stomach and duodenum, possibly change in gallbladder) by use of ultrasonography and MRI might be useful for the prenatal diagnosis of such cases.
Dysthymic Reactions of Women Undergoing Chorionic Villus Sampling for Prenatal Diagnosis of Hemoglobinopathies or Karyotyping
Authors: Lykeridou Katerina , Daskalakis George , Papadatou Danai , Vaslamatzis Grigoris , Dafni Ourania , Antsaklis Aris
Published: February 2004

Objectives: The aim of the study was to investigate the levels of anxiety and depression, as well as liability to depression, of women undergoing chorionic villus sampling (CVS) due to the risk of giving birth to a child suffering from hemoglobinopathy, or trisomy. Methods: The study population consisted of 309 women who attended the Fetal Medicine Unit of Alexandra Hospital, University of Athens, Athens, Greece for a first trimester chorionic villus sampling (CVS). One hundred and fifty-nine women (group A) underwent CVS due to increased possibility of carrying an embryo with β-thalassemia, while 150 women had the procedure because of an increased nuchal translucency measurement, or a positive first trimester biochemical screening (group B). Three hundred and nine women, matched by age and gestational age with those of the study group, who were not subjected to any diagnostic intervention formed the control group. We further investigated differences of dysthymic reactions among three subgroups of women at risk for hemoglobinopathy: (a) women undergoing their first pregnancy; (b) women who had been pregnant more than once but had not any children, and (c) women who had given birth to at least one healthy child, irrespective of previous terminations. Results: The incidence of clinically elevated levels of anxiety and depression was significantly higher in groups A and B compared to controls (p < 0.001), while no significant difference was found in mean anxiety and depression, as well as the liability to depression among the three groups. Clinically elevated levels of depression were found in 10.1 and 4.7% of the women of the hemoglobinopathy and karyotyping group, respectively. Especially women who had no children, due to previous pregnancy terminations presented significantly higher incidence of elevated depression compared to women who were pregnant for the first time, or women who had given birth to at least one healthy child in their life. Conclusions: The findings of this study highlight the necessity of training medical and nursing personnel to understand and respond to the psychological and social needs of women undergoing CVS due to increased risk for hemoglobinopathy, and especially to those who have no children and who have a history of pregnancy termination due to an affected fetus.
Prenatal Diagnosis of a ‘Minor’ Form of Brachmann-de Lange Syndrome by Three-Dimensional Sonography and Three-Dimensional Computed Tomography
Authors: Le Vaillant Claudine , Quere Marie-Pierre , David Albert , Berlivet Marc , Boog Georges
Published: February 2004

Brachmann-de Lange syndrome is a congenital disease characterized by severe mental retardation, pre- and postnatal symmetric growth delay, limb defects, visceral anomalies, hirsutism, and a typical face. The authors describe the prenatal sonographic pattern of Brachmann-de Lange syndrome suspected at 20 weeks of gestation, with severe intrauterine growth retardation, facial dysmorphism, cardiac abnormality, and micromelia without the typical defects of the upper limbs. Fetal karyotyping was normal. The diagnosis of a ‘minor’ form of Brachmann-de Lange syndrome was confirmed at 28 weeks of gestation by using three-dimensional sonography in order to assess precisely the facial dysmorphism and by performing a three-dimensional computed tomography of the upper limbs in order to identify the subtle abnormalities of the radial head and of the first metacarpal bone.
Prenatal Maternal Stress, Prenatal Fetal Movements and Perinatal Temperament Factors Influence Behavior and School Marks at the Age of 6 Years
Authors: Niederhofer Helmut , Reiter Alfons
Published: February 2004

Niederhofer showed in 1994 that maternal stress during pregnancy seemed to be associated with temperament in early childhood. This study examined the correlation between maternal stress during pregnancy in 227 women, ultrasound observation of intrauterine fetal movements, the child’s temperament in early childhood, and the child’s school marks at the age of 6 years. Our results show a significant correlation between prenatal maternal stress, perinatal temperament of the child and his/her school marks at the age of 6 years. Only intrauterine fetal movements were associated neither with stress during pregnancy nor with early personality.
Antenatal Diagnostic Aspects of Unilateral Multicystic Kidney Dysplasia – Sensitivity, Specificity, Predictive Values, Differential Diagnoses, Associated Malformations and Consequences
Authors: Eckoldt Felicitas , Woderich R. , Smith R.D. , Heling K.-S.
Published: February 2004

Objectives: Unilateral multicystic kidney dysplasia (MCKD) is the second most common urinary tract abnormality diagnosed antenatally. Whilst an isolated unilateral MCKD has a good prognosis, a poor outcome must be expected when MCKD is associated with other complex abnormalities. Material: Out of 11,176 cases, 693 fetuses were suspected of having urinary tract abnormalities. Urological findings were confirmed in 548 of them. Unilateral cystic kidney was diagnosed prenatally in 85 cases. Results: The study results in a total of 107 cases with proven MCKD. Eighty-five pregnancies with a prenatal diagnosis of MCKD were analysed. The antenatal diagnosis of MCKD was confirmed in 56 cases. Fifty-one children were found to have unilateral MCKD where this had not been explicitly suspected from antenatal scanning. Conclusion: Unilateral MCKD is a malformation with an excellent prognosis for child survival and global renal function if encountered in isolation. However, our analysis of live infants and autopsy cases demonstrates a high proportion of severe associated malformations of the urinary tract and other organ systems.
Pericardial Hemangioma Presenting as Thoracic Mass in utero
Authors: Puligandla P.S. , Kay S. , Morin L. , Desilets V. , Jutras L. , Shum-Tim D. , Bernard C. , Flageole H.
Published: February 2004

Pericardial hemangiomas are rare lesions. We present the case of an infant who was referred to our fetal diagnosis and treatment group for the presence of a left thoracic mass, pleural effusion, and mediastinal shift on fetal ultrasound. The characteristics of the lesion suggested the presence of a pulmonary sequestration. A chest radiograph done at birth was normal. At 2 weeks of age, an enhancing lesion of the left pericardium was identified on chest CT. A cardiac MRI demonstrated enhancement of the mass on T2-weighted images. The patient underwent thoracoscopic assessment of the mass for diagnostic purposes. Multiple lesions were identified along the left pericardium and diaphragm. A frozen section biopsy revealed a hemangioma. The natural history for hemangiomas is gradual regression; however, they may increase acutely in size and cause symptoms prior to involution. Investigations should be performed to identify the involvement of other organs. This case illustrates the need to closely follow all patients with prenatally diagnosed thoracic masses with CT imaging, even when they are asymptomatic and have a normal chest radiograph at birth.
Maternal Mortality following Diagnostic 2nd-Trimester Amniocentesis
Authors: Elchalal Uriel , Shachar Inbar Ben , Peleg Dan , Schenker Joseph G.
Published: February 2004

We present 2 cases of maternal mortality after transabdominal amniocentesis performed during the 2nd trimester of pregnancy. In both these cases, blood cultures revealed Escherichia coli. Broad-spectrum intravenous antibiotic treatment started immediately after admission to the hospital did not change the rapid progression of the disease. Despite evacuation of the uterus within <10 h from the diagnosis of septic abortion and transfer to the intensive care units to treat multiorgan failure, these patients died. Septic abortion and septic shock following transabdominal amniocentesis are very rare; however, they carry a serious risk to the patients’ life. The combination of fever and leukopenia several days after amniocentesis should alert the physician to the evolution of sepsis. Because of the risk involved, information given to the patient prior to amniocentesis should refer to possible fetal complications and to the remote possibility of maternal risks as well.
Multiplex Nested PCR for Preimplantation Genetic Diagnosis of Spinal Muscular Atrophy
Authors: Malcov Mira , Schwartz Tamar , Mei-Raz Nava , Yosef Dalit Ben , Amit Ami , Lessing Joseph B. , Shomrat Ruth , Orr-Urtreger Avi , Yaron Yuval
Published: February 2004

Objective: Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder caused in most patients by homozygous deletion of the SMN1 gene. For a carrier couple at a 25% risk of affected offspring, preimplantation genetic diagnosis (PGD) offers an alternative to prenatal diagnosis and termination of affected pregnancies. Our objective was to develop an accurate and reliable single-cell multiplex nested PCR analysis for PGD of SMA. Methods: The method was developed on single blood leukocytes, obtained from healthy controls and an adult SMA type III patient with a known homozygous deletion of SMN1 exon 7 and 8. Multiplex nested PCR on single cells was used to co-amplify exons 7 and 8 of SMN. Additional multiplexing was performed with the ZFX/ZFY gene for sexing. Following successful establishment of the multiplex nested PCR protocol in single leukocytes, the technique was employed for PGD in 4 patients for a total of 7 cycles. In 2 patients, sexing was simultaneously performed using ZFX/ZFY. Results: 220 single leukocytes from a normal individual and 220 from an SMA patient were analyzed. Exon 7 of SMN1 was amplified in 99% of normal single leukocytes and in none of the SMA-affected leukocytes. Exon 7 of SMN2 was amplified in 100% of both normal and SMA-affected leukocytes. Exon 8 of SMN1 was amplified in 98% of normal cells and in none of the SMA-affected leukocytes. Exon 8 of SMN2 was amplified in 96% of both normal and SMA-affected leukocytes. Amplification efficiency was 99% for ZFX/ZFY. There were no false-negative results and no contamination was detected in all wash-drop blanks tested. Seven PGD cycles were performed in 4 SMA-carrier couples with successful molecular analysis of 34 embryos and a total of 15 normal embryos transferred in 7 cycles. One clinical pregnancy has resulted in the delivery of a healthy male. Amniocentesis performed at 17 weeks confirmed the correct diagnosis for both SMA and sexing. Conclusions: These results suggest that our multiplex nested PCR protocol offers an efficient and accurate method for PGD of SMA while enabling the simultaneous analysis of an additional loci.