Simultaneous inhibition of the retrotrapezoid nucleus (RTN) and raphe obscurus (ROb) decreased the systemic CO(2) response by 51%, an effect greater than inhibition of RTN (-24%) or ROb (0%) alone, suggesting that ROb modulates chemoreception by interaction with the RTN (19). We investigated this interaction further by simultaneous dialysis of artificial cerebrospinal fluid equilibrated with 25% CO(2) in two probes located in or adjacent to the RTN and ROb in conscious adult male rats. Ventilation was measured in a whole body plethysmograph at 30 degrees C. There were four groups (n = 5): 1) probes correctly placed in both RTN and ROb (RTN-ROb); 2) one probe correctly placed in RTN and one incorrectly placed in areas adjacent to ROb (RTN-peri-ROb); 3) one probe correctly placed in ROb and one probe incorrectly placed in areas adjacent to RTN (peri-RTN-ROb); and 4) neither probe correctly placed (peri-RTN-peri-ROb). Focal simultaneous acidification of RTN-ROb significantly increased ventilation (Ve) up to 22% compared with baseline, with significant increases in both breathing frequency and tidal volume. Focal acidification of RTN-peri-ROb increased Ve significantly by up to 15% compared with baseline. Focal acidification of ROb and peri-RTN had no significant effect. The simultaneous acidification of regions just outside the RTN and ROb actually decreased Ve by up to 11%. These results support a modulatory role for the ROb with respect to central chemoreception at the RTN.
Neonatal rodents deficient in medullary serotonin neurons have respiratory instability and enhanced spontaneous bradycardias. This study asks if, in Pet-1(-/-) mice over development: 1) the respiratory instability leads to hypoxia; 2) greater bradycardia is related to the degree of hypoxia or concomitant hypopnea; and 3) hyperthermia exacerbates bradycardias. Pet-1(+/+), Pet-1(+/-), and Pet-1(-/-) mice [postnatal days (P) 4-5, P11-12, P14-15] were held at normal body temperature (T(b)) and were then made 2 degrees C hypo- and hyperthermic. Using a pneumotach-mask system with ECG, we measured heart rate, metabolic rate (Vo(2)), and ventilation. We also calculated indexes for apnea-induced hypoxia (total hypoxia: apnea incidence x O(2) consumed during apnea = microl.g(-1).min(-1)) and bradycardia (total bradycardia: bradycardia incidence x magnitude = beats missed/min). Resting heart rate was significantly lower in all Pet-1(-/-) animals, irrespective of T(b). At P4-5, Pet-1(-/-) animals had approximately four- to eightfold greater total bradycardia (P < 0.001), owing to an approximately two- to threefold increase in bradycardia magnitude and a near doubling in bradycardia incidence. Pet-1(-/-) animals had a significantly reduced Vo(2) at all T(b); thus there was no genotype effect on total hypoxia. At P11-12, total bradycardia was nearly threefold greater in hyperthermic Pet-1(-/-) animals compared with controls (P < 0.01). In both genotypes, bradycardia magnitude was positively related to the degree of hypopnea (P = 0.02), but there was no genotype effect on degree of hypopnea or total hypoxia. At P14-15, genotype had no effect on total bradycardia, but Pet-1(-/-) animals had up to seven times more total hypoxia (P < 0.001), owing to longer and more frequent apneas and a normalized Vo(2). We infer from these data that 1) Pet-1(-/-) neonates are probably not hypoxic from respiratory dysfunction until P14-15; 2) neither apnea-related hypoxia nor greater hypopnea contribute to the enhanced bradycardias of Pet-1(-/-) neonates from approximately P4 to approximately P12; and 3) an enhancement of a temperature-sensitive reflex may contribute to the greater bradycardia in hyperthermic Pet-1(-/-) animals at approximately P12.
Kainic acid (4.7 mM) applied to the rostral ventrolateral medulla (RVLM) surface decreases phrenic output, CO2 sensitivity, and blood pressure in chloralose-urethan-anesthetized, vagotomized, paralyzed, glomectomized, servoventilated cats. In this study using the same preparation, bilateral 50- to 100-nl kainate injections just below the RVLM surface better localized these responses topographically. The physiological responses to unilateral 10-nl kainate injections were then correlated with anatomic location determined by fluorescent microbeads (0.5 micron diam). Many sites were associated with no effect, a few rostral and caudal sites with increased phrenic activity, and cluster of sites with decreased phrenic activity often to apnea, decreased CO2 sensitivity, and decreased responses to carotid sinus nerve stimulation. Blood pressure was unaffected. These sites, within 400 microns of the surface, were ventral to the facial nucleus, ventrolateral to the nucleus paragigantocellularis lateralis, caudal to the superior olive, and rostral to the retrofacial nucleus. They appeared to be within the recently described retrotrapezoid nucleus, which contains cells with respiratory-related activity and projections to the dorsal and ventral respiratory groups. Cells within this site appear able to provide tonic input to respiration and to affect peripheral and central chemoreception.
No direct comparison of tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) has yet been carried out in the treatment of liver cirrhosis in China. We designed a double-blind randomized trial to evaluate the potential therapeutic efficacy of TUDCA in liver cirrhosis, using UDCA as parallel control. The enrolled 23 patients with liver cirrhosis were randomly divided into TUDCA group (n=12) and UDCA group (n=11), and given TUDCA and UDCA respectively at the daily dose of 750 mg, in a randomly assigned sequence for a 6-month period. Clinical, biochemical and histological features, and liver ultrasonographic findings were evaluated before and after the study. According to the inclusion criteria, 18 patients were included in the final analysis, including 9 cases in both two groups. Serum ALT, AST and ALP levels in TUDCA group and AST levels in UDCA group were significantly reduced as compared with baseline (P<0.05). Serum albumin levels were significantly increased in both TUDCA and UDCA groups (P<0.05). Serum markers for liver fibrosis were slightly decreased with the difference being not significant in either group. Only one patient in TUDCA group had significantly histological relief. Both treatments were well tolerated and no patient complained of side effects. It is suggested that TUDCA therapy is safe and appears to be more effective than UDCA in the treatment of liver cirrhosis, particularly in the improvement of the biochemical expression. However, both drugs exert no effect on the serum markers for liver fibrosis during 6-month treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.