Biomedical subjects

F G Smith

Publications and source records attributed to F G Smith.

At least 37 records · Page 2Linked to original sources

PubMed1997

Dose-dependent cardiovascular, renal, and endocrine effects of furosemide in conscious lambs.

In recent experiments in conscious lambs, we showed that in addition to its well-known natriuretic and diuretic effects, i.v. injection of 2 mg/kg of furosemide resulted in a sustained increase in heart rate and an age-dependent increase in plasma renin activity. To determine whether these responses were dose dependent, we measured various parameters of cardiovascular, renal, and endocrine function in six chronically instrumented lambs. Three of seven doses of furosemide were tested at 48-h intervals; the range of doses was 0 to 7.5 mg/kg. A dose-dependent transient pressor response occurred within 20 min of furosemide administration; the duration of this response increased with increasing doses. Heart rate increased 40 min after doses of furosemide > or = 0.25 mg/kg; this response was not dose dependent. Renin increased following all doses; the peak and the duration of the renin response were dose dependent. These data provide new information on the dose-dependent cardiovascular, renal, and endocrine responses to furosemide in conscious newborn lambs.

Aldosterone↗

PubMed1996

Met-enkephalin Arg-Phe-immunoreactive neurons in the central nervous system of the pond snail Lymnaea stagnalis.

The distribution of an opioid peptide related to YGGFMRF was determined in the CNS and other organs of the pond snail, Lymnaea stagnalis, by RIA and immunocytochemistry. RIA revealed the highest levels in the CNS (1 pmol/organ) and penis (400 fmol/organ). There were also significant levels in the haemolymph, most of which was not associated with haemocytes (580 fmol/ml). Both serial section and whole-mount immunocytochemistry of the CNS revealed immunoreactive cells in every ganglion with the majority in the cerebral and pedal ganglia. In the pedal ganglia some of the immunoreactive cells were close to the cells of the A-cluster, which are known to respond to opioids, and could innervate them. In the cerebral ganglia the immunoreactive cells included a group of neurosecretory cells, the caudo dorsal cells (CDCs) and the terminals of these cells in the cerebral commissure were also stained. The CDCs secrete peptides into the haemolymph and so could be the source of the YGGFMRF immunoreactivity. Immunoreactivity (including the CDCs) was observed in locations that correspond to those reported for other fragments of proenkephalin, such as Met- and Leu-enkephalin, suggesting that they may share a common precursor, a Lymnaea proenkephalin. A map of the 358 YGGFMRF-immunoreactive cells in the CNS is presented, many of which have not been previously identified.

Amino Acid Sequence↗

PubMed1996

Cardiovascular, renal, and endocrine responses to graded volume expansion in lambs during maturation.

To further investigate the maturation of the cardiopulmonary baroreflex, we measured the effects of a 45-min blood volume expansion to an increase in right atrial pressure of approximately 4 mmHg in chronically instrumented newborn (n = 17) and older lambs (n = 14). Measurements included various parameters of endocrine, cardiovascular, and renal function and concomitant recording of renal sympathetic nerve activity (RSNA). During blood volume expansion, RSNA was inhibited to a similar extent in newborns and older lambs when atrial pressures were increased by approximately 4 mmHg. A sympathoinhibition persisted in newborns but was only transient in older lambs. In newborn lambs, heart rate decreased in response to blood volume expansion, whereas heart rate remained constant after blood volume expansion in older lambs. The renal and endocrine responses to blood volume expansion were, however, similar in newborns and older lambs. These data provide evidence that when atrial pressures are matched, the renal and endocrine responses to blood volume expansion are similar, but there are differential cardiovascular and RSNA responses. Any reduced ability of the newborn kidney to excrete a volume load is therefore probably related to maturational differences in its distribution between the capacitance vessels and the heart.

Aging↗

PubMed1996

Renal nerves do not modulate the renal and endocrine responses to furosemide in conscious lambs.

To test the hypothesis that renal sympathetic nerves influence the renal and renin responses to furosemide in conscious newborn animals, experiments were carried out in chronically instrumented lambs with either bilateral renal denervation (denervated, n = 7, age = 13 +/- 3 (SD) days) or intact renal sympathetic nerves (intact, n = 6, age = 13 +/- 4 (SD) days), at least 4 days after surgery. Basal glomerular filtration rate (GFR), urinary flow, and sodium excretion rates were similar in intact and denervated lambs (p > 0.5). A prompt diuretic and natriuretic response and a decrease in GFR occurred after i.v. furosemide (2 mg/kg); these responses were similar in intact and denervated lambs. Basal plasma renin activity (PRA) was not altered by renal denervation. PRA increased 10 min after furosemide (p < 0.001) and remained elevated at 90 min; the response was similar in both groups of lambs. Basal plasma aldosterone levels were elevated in denervated (191 +/- 232 (SD) pg/mL) compared with intact lambs (62 +/- 24 (SD) pg/mL). Plasma aldosterone levels increased after furosemide administration in both groups of animals. These data provide evidence to suggest that renal sympathetic nerves do not appear to modulate the renal and endocrine responses to furosemide, at least at a dose of 2 mg/kg. Our observations also support the premise that early in life, aldosterone counteracts the effects of renal denervation on fluid and electrolyte homeostasis.

Aldosterone↗

PubMed1995

Renal and renin responses to furosemide in conscious lambs during postnatal maturation.

Despite the widespread use of furosemide in the treatment of various fluid and electrolyte disorders in the preterm and term human infant and child, the physiological effects of this potent diuretic agent on renal function and renin release during postnatal maturation are poorly understood. To test the hypothesis that the renal and renin responses to furosemide are altered during postnatal maturation, experiments were carried out in conscious chronically instrumented newborn lambs (11 +/- 3 days, n = 7) and older lambs (28 +/- 3 days, n = 6), at least 5 days after surgery under halothane anesthesia for placement of catheters. Renal function and plasma renin activity (PRA) were measured for 1 h before and 2 h after intravenous injection of furosemide (2 mg/kg; 0.2 mL/kg) or vehicle (0.2 mL/kg). Glomerular filtration rate (GFR) decreased after furosemide administration to both groups of lambs. However, the time course of this decrease in GFR was different, occurring sooner in older lambs (30 min) than in newborns (90 min). GFR remained significantly decreased after 150 min in both age-groups. The natriuretic and diuretic responses to furosemide were similar in newborns and older lambs, peak diuretic and natriuretic responses occurring within 30 min. PRA increased dramatically in both age-groups after furosemide; the response was accentuated in newborns. After 2 h, PRA was still elevated in newborns but returned towards control levels in older lambs. These data demonstrate that both the GFR and renin responses to furosemide are altered during ontogeny.

Animals↗

PubMed1995

Effects of renal denervation on cardiovascular response to furosemide in conscious lambs.

The cardiovascular response to furosemide in the newborn and the role of renal sympathetic nerves in influencing this response have not been investigated. We hypothesized that in conscious lambs, furosemide would decrease blood pressure, the response being accentuated in the absence of renal sympathetic nerves. Pulsatile pressures and heart rates were measured before and after furosemide (2 mg/kg) administration to chronically instrumented lambs with either bilateral renal denervation (denervated, n = 8) or renal nerves intact (intact, n = 6). In intact lambs, mean arterial pressure remained constant after furosemide; in denervated lambs there was an increase in arterial pressure 20 min after furosemide (P < 0.001), and control levels were reached by 100 min. Basal heart rate was higher in denervated than in intact lambs (P = 0.009). In both groups of lambs, heart rate increased 40 min after furosemide and remained elevated. These data provide new information that, in conscious newborn animals, renal sympathetic nerves influence the blood pressure response to furosemide, as well as basal control of heart rate.

Animals↗

PubMed1994

Functional morphology of the light yellow cell and yellow cell (sodium influx-stimulating peptide) neuroendocrine systems of the pond snail Lymnaea stagnalis.

Neuroendocrine light yellow cells of the pond snail Lymnaea stagnalis express a neuropeptide gene encoding three different peptides. The morphology of the cell system has been studied by in situ hybridization, using two synthetic oligonucleotides encoding parts of light yellow cell peptides I and III, and by immunocytochemistry with antisera to synthetic light yellow cell peptide II and to two fragments of light yellow cell peptide I. One large cluster of light yellow cells was observed in the ventro-lateral protrusion of the right parietal ganglion, smaller clusters lying in the posterior dorsal part of this ganglion and in the visceral ganglion. The cells had an extended central neurohaemal area. Immunopositive axons projected into all nerves of the ganglia of the visceral complex, into the superior cervical and the nuchal nerves, and into the connective tissue surrounding the central nervous system. Axon tracts ramified between the muscle cells of the walls of the anterior aorta and of smaller blood vessels. Peripheral innervation by the light yellow cell system was only found in muscular tissue of the ureter papilla. The antisera to the two peptide fragments of light yellow cell peptide I not only stained the light yellow cells, but also the identified yellow cells, which have previously been shown to produce the sodium influx-stimulating neuropeptide. The latter cells were negative to the in situ hybridization probes and antisera specific to the light yellow cell system. It is therefore unlikely that the yellow cells express the light yellow cell neuropeptide gene. Nevertheless, the cells contain a neuropeptide sharing antigenic determinants with light yellow cell peptide I.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1993

Correlation between PCNA and AgNOR scores in non-Hodgkin's lymphomas using sequential staining technique.

AIMS: To investigate the relation between the numbers of interphase silver stained nucleolar organiser regions (AgNORs) and immunolabelling with the monoclonal antibody PC10, which demonstrates proliferating nuclei by reacting with proliferating cell nuclear antigen (PCNA). METHODS: The established sequential technique for the demonstration of interphase AgNORs and of antigens in paraffin wax sections was applied to a small series of non-Hodgkin's lymphomas (NHL) of both low and high grade type, together with specimens of palatine tonsil. The numbers of PCNA positive cells were counted in all specimens; in the tonsils the cells were counted in both follicle centres and in the interfollicular areas. The numbers of AgNORs in both PCNA positive and PCNA negative nuclei were then counted. RESULTS: Lower numbers of PCNA positive cells were found in the low grade than the high grade NHL (18-28.4% and 34.2-51.3%, respectively). This was reflected in the two areas of the palatine tonsils, the counts being higher in the follicle centre nuclei than in those in the interfollicular compartments. In general, the numbers of AgNORs were higher in the PCNA positive nuclei than in those lacking the antigen; however, a consistent finding was that relatively high AgNOR scores were observed in PCNA negative nuclei, especially in the high grade lymphomas. In the tonsils, however, the AgNOR counts were much lower in the nuclei lacking PCNA than in those containing it. CONCLUSIONS: The results obtained in the lymphomas were rather unexpected as, in general, previous studies have shown a close direct or indirect relation between AgNOR scores and proliferating cell counts. An explanation for these findings may be that the argyrophil proteins associated with proliferating cells remain in the nucleus in detectable form longer than the PCNA antigen, at least in neoplastic tissue.

Antigens, Neoplasm↗

PubMed1992

Mechanisms regulating renal sodium excretion during development.

The present review focuses on the ontogeny of mechanisms involved in renal sodium excretion during renal maturation. The effect of birth on renal excretion of sodium and the role played by the different tubular segments in the regulation of sodium excretion during maturation are discussed. The influence of circulating catecholamines and renal sympathetic innervation in regulating sodium excretion during renal development is reviewed. The effects of aldosterone, atrial natriuretic factor, and prostaglandins on sodium regulation during renal maturation are discussed. Special emphasis is given to the potential role of glucocorticoids in modulating sodium excretion early in life.

Aldosterone↗

PubMed1992

Analgesic efficacy of bromfenac, ibuprofen, and aspirin in postoperative oral surgery pain.

We recently demonstrated that 25 mg of bromfenac, a new nonsteroidal anti-inflammatory analgesic, is at least as effective as 400 mg of ibuprofen in relieving postoperative oral surgery pain. Our objective in this study was to determine whether higher doses were significantly more effective. Two hundred eighty (280) outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, a single oral dose of 10, 25, 50, or 100 mg bromfenac; 650 mg aspirin; 400 mg ibuprofen; or placebo. Subjects rated their pain and its relief for 8 hours. All active treatments were significantly superior to placebo, and bromfenac and ibuprofen were significantly superior to aspirin. The slope of the dose-response curve of bromfenac was significant. The 100 mg bromfenac dose was significantly more effective than the 400 mg ibuprofen dose and had a significantly longer duration of analgesic action.

Aspirin↗

PubMed1992

Renal nerves modulate kidney renin gene expression during the transition from fetal to newborn life.

The role of renal nerves in regulating changes in plasma renin activity (PRA) and renal renin gene expression was studied in intact (n = 6) and denervated (n = 6) fetal sheep before birth and during the first 24 h after delivery. Renal denervation completely blunted the rise in PRA observed 24 h after delivery in newborn lambs; in lambs with intact kidneys, PRA increased significantly (P less than 0.05) from 3.26 +/- 0.60 (predelivery) to 6.34 +/- 1.85 ng angiotensin I (ANG I).ml-1.h-1 (24 h postdelivery), while in lambs with denervated kidneys, predelivery and post-delivery values were 2.84 +/- 0.19 and 2.49 +/- 0.45 ng ANG I.ml-1.h-1, respectively. Renin mRNA levels were significantly lower (P less than 0.001) in denervated than in intact kidneys 24 h after birth. A close analysis of these results also revealed that renin mRNA levels were significantly higher (P less than 0.001) in intact kidneys of newborn lambs delivered vaginally (n = 3) than in newborn lambs delivered by cesarean section (n = 3). These results suggest that renal nerves play an important role in regulating renin gene expression and PRA during the transition from fetal to newborn life.

Aging↗

PubMed1992

Effects of volume expansion on renal sympathetic nerve activity and cardiovascular and renal function in lambs.

To assess the cardiopulmonary baroreflex in the immature animal, effects of volume expansion on changes in right atrial pressure, renal sympathetic nerve activity, and renal function were measured in chronically instrumented newborn (4-8 days; n = 13) and older lambs (4-5 wk; n = 14). Studies were carried out for 30 min before and 2 h after volume expansion with 6% Dextran 70 (25 ml/kg). Right atrial pressure increased by 4.0 +/- 0.5 mmHg in newborns and by 8.8 +/- 0.6 mmHg in older lambs within 15 min of volume expansion (P less than 0.001). After volume expansion, heart rate decreased in newborns from 237 +/- 6 beats/min to a nadir of 211 +/- 7 beats/min 2 h later (P less than 0.001) but remained constant at control levels of 148 +/- 9 beats/min in older lambs. Maximal inhibition of renal sympathetic nerve activity was achieved at 15 min in older lambs (-50.1 +/- 7.5%) and at 60 min (-58.3 +/- 10.9%) in newborns in which there was a prolonged sympathoinhibition (P less than 0.001). There was also a significant diuretic response in both groups but a limited natriuretic response to volume expansion in newborns (P greater than 0.05) compared with older lambs (P less than 0.001). These data demonstrate the presence of the cardiopulmonary baroreflex in the first week of life in lambs. The sustained sympathoinhibition and bradycardia seen in response to volume expansion in newborns but not in older lambs support the hypothesis that the reflexes controlling arterial pressure and blood volume change with postnatal maturation.

Animals↗

PubMed1992

Ontogeny of renal response to specific dopamine DA1-receptor stimulation in sheep.

The present study was designed to characterize the developmental changes in the renal responses to dopamine DA1-receptor activation in chronically instrumented preterm (109-115 days) and near-term (130-140 days, full term 145 days) fetal sheep. Cumulative doses of the selective DA1-agonist fenoldopam increased mean arterial blood pressure (MABP) in both preterm (+16 +/- 3%) and near-term fetuses (+16 +/- 3%) but had no significant effect on renal blood flow velocity. Infusion of the DA1-antagonist SCH-23390 did not affect the increase in MABP, suggesting that the effect of fenoldopam on MABP was not directly related to activation of DA1-receptors. Fenoldopam infusion had no significant effects on renal function parameters in preterm fetuses. In near-term fetuses, however, fenoldopam increased urinary flow rate (82.6 +/- 20.9%, P < 0.003), glomerular filtration rate (GFR; 16.6 +/- 4.9%, P < 0.01), urinary sodium excretion (40.1 +/- 14.9%, P < 0.02), and fractional excretion of sodium (26.8 +/- 11.2%, P < 0.03). Infusion of the DA1-antagonist SCH-23390 blocked the fenoldopam-induced diuresis and natriuresis but had no significant effect on the rise in GFR. Fenoldopam infusion had no significant effects on plasma renin activity and plasma aldosterone concentration and on urinary prostaglandin (PG) excretion (PGE2, PGF2 alpha, and 6-keto-PGF1 alpha). Taken together, these results suggest that the renal effect of DA1-receptor activation is age dependent and that stimulation of DA1-receptor in near-term fetuses is associated with a diuresis and natriuresis that seem to be independent of renal hemodynamics and adrenal effects.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1992

Regulation of sodium metabolism and extracellular fluid volume during development.

In addition to regulating developmental changes in body fluid content, the newborn kidney must maintain a positive sodium balance to ensure adequate body growth. Mechanisms by which the developing organism perceives changes in volume and the manner in which the kidney responds to these changes have been reviewed. Perception of changes in ECF volume is sensed by volume receptors that involve central nervous system signal processing (e.g., low- and high-pressure volume receptors) before influencing the kidney by way of the renal nerves or that are directly coupled with the kidney and do not involve central nervous system processing (e.g., juxtaglomerular apparatus, ANF, hepatic factors). Results presently available demonstrate that these mechanisms are functional early in life and that their sensitivity changes during development in accordance with the needs of the organism. In addition, the developing kidney has unique characteristics that allow it to maintain a positive sodium balance necessary for growth.

Adult↗

PubMed1991

Zinc absorption in women: comparison of intrinsic and extrinsic stable-isotope labels.

Fractional absorption of extrinsic and intrinsic zinc from milk-based formulated diets was measured in 10 young women by using a simultaneous triple-isotope method based on fecal monitoring of unabsorbed enriched stable-isotope labels. Zinc intake was held nearly constant (mean zinc intake = 1.48 mumol.kg body wt-1.d-1) throughout the 18-d controlled feeding phase of the study by addition of extrinsic 64Zn to all formula feedings, with substitution of the extrinsic 67Zn label for some of the 64Zn when formula intrinsically labeled with 70Zn was given. Fractional absorption values of intrinsic and extrinsic zinc labels, 0.267 +/- 0.092 (mean +/- SD) and 0.282 +/- 0.086, respectively, were highly correlated (r = 0.83, P less than 0.05) and did not differ significantly. The ratio of fractional absorption of the extrinsic to that of the intrinsic label, 1.08 +/- 0.20 (mean +/- SD), was not significantly different from unity. The results show that extrinsic labeling by use of enriched stable isotopes is a valid means of determining zinc absorption from milk-based diets in adult humans.

Absorption↗

PubMed1991

Role of renal sympathetic nerves in lambs during the transition from fetal to newborn life.

To determine the role of renal sympathetic nerves in influencing renal function during the transition from fetal to newborn life, studies were carried out in conscious, chronically instrumented fetal sheep with either bilateral renal denervation (n = 11) or intact renal nerves (n = 12), 3-6 d after surgery. Endocrine, renal, and cardiovascular parameters were measured before and after delivery of lambs by cesarean section. Blood pressure and heart rate were similar in intact and denervated fetuses, and increased after delivery in both groups. There was also a transient diuresis and natriuresis, in the immediate postnatal period, the response being significantly greater in denervated than intact lambs (P less than 0.05). By 24 h postnatally, fluid and electrolyte excretions were similar in both groups, and significantly less than fetal levels. In the absence of renal nerves, the normal rise in plasma renin activity at birth was attenuated. These data provide evidence that renal sympathetic nerves play an important role during the transition from fetal to newborn life, and support the premise that birth is associated with sympathetic activation.

Animals↗

PubMed1991

Endocrine effects of ventilation, oxygenation and cord occlusion in near-term fetal sheep.

The transition from fetal to newborn life is associated with significant endocrine changes. Some of these changes may be triggered by the effects of spontaneous respiration, increased oxygenation and removal of the placental circulation at birth. We, therefore, studied endocrine function during in utero ventilation, oxygenation and cord occlusion, in nine chronically-instrumented fetal sheep aged 137 to 140 days of gestation. During the sequential effects of in utero ventilation and oxygenation, plasma renin activity (PRA) and angiotensin II (AII) remained at control levels of 6.3 +/- 1.9 ng/ml per h and 66 +/- 15 pg/ml. After cord occlusion, PRA increased to 10.3 +/- 2.2 ng/ml per hr and AII increased to 86 +/- 24 pg/ml, the latter being non-significant. Plasma cortisol levels also increased from control levels of 3.5 +/- 1.0 to 6.7 +/- 0.8 g/dl during cord occlusion (P = 0.02). During the sequential effects of ventilation, oxygenation and cord occlusion, plasma epinephrine increased from control levels of 87 +/- 17 to 492 +/- 142 pg/ml (P = 0.04), and plasma norepinephrine levels increased slightly from 620 +/- 112 to 850 +/- 214 pg/ml. These data provide evidence that many of the changes in endocrine function seen at birth result from factors other than spontaneous respiration, oxygenation and umbilical cord occlusion.

Air↗

PubMed1991

Evaluation of bromfenac, aspirin, and ibuprofen in postoperative oral surgery pain.

Two hundred forty-one outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive a single oral dose of bromfenac 5, 10, or 25 mg, aspirin 650 mg, ibuprofen 400 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief for 8 hours after medicating. Estimates of summed pain intensity difference, peak pain intensity difference, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active treatments were significantly superior to placebo, and the slope of the dose-response curve for bromfenac was significant. Bromfenac 5 mg and aspirin 650 mg were equianalgesic; bromfenac 25 mg was slightly more efficacious than ibuprofen 400 mg. Bromfenac 25 mg and ibuprofen 400 mg were significantly superior to the other active treatments. Adverse effects were transient and consistent with the pharmacologic profiles of the medications evaluated.

Administration, Oral↗