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Biomedical subjects

R J Martin

Publications and source records attributed to R J Martin.

At least 289 records · Page 16Linked to original sources
PubMed1991

Metabolic development of liver and adipose tissue in pre-obese and control pig fetuses.

The metabolic development of the liver and adipose tissue was examined in 75 and 110 day fetuses from genetically obese and control sows. In the liver, glucose and palmitate utilization was influenced by both age and strain. Higher rates of glucose oxidation and palmitate oxidation and esterification were observed in the 75 day compared to the 110 day fetuses. Hepatic palmitate oxidation was greater in pre-obese than in control fetuses at both fetal ages, while hepatic palmitate esterification was greater in pre-obese than in control fetuses at 75 days of gestation only. In subcutaneous adipose tissue, de novo lipogenesis increased with age and was higher in pre-obese than in control fetuses by 110 days of gestation. At 75 days of gestation, glucose oxidation and incorporation into fatty acids was similar in adipose tissue from both strains. However, by 110 days of gestation, both basal and insulin-stimulated rates of glucose metabolism were greater in pre-obese compared to control fetuses. Palmitate esterification increased with age but was similar in pre-obese and control fetuses. Basal lipolysis was not affected by strain or age. Isoproterenol had no effect on lipolysis in the 75 day fetuses while stimulating glycerol release to a comparable degree in 110 day fetuses of both strains. This study demonstrates that metabolic differences between genetically obese and control pigs are already apparent in the pre-obese state prior to birth. Such alterations in hepatic and adipose tissue carbohydrate and lipid metabolism, which promote early lipid storage by the pre-obese fetuses, may serve as useful metabolic markers for the development of obesity.

Adipose Tissue↗
PubMed1990

Alterations in the binding characteristics of glucocorticoid receptors from obese Zucker rats.

Obese Zucker rats appear to lack a circadian rhythm of serum corticosterone and maintain relatively high concentrations throughout the 24-h day. The binding characteristics of glucocorticoid receptors in lean and obese Zucker rats were examined in three tissues suggested to be involved in the feedback inhibition of corticosterone: the anterior pituitary, hypothalamus and hippocampus. Hepatic glucocorticoid receptors were also examined to determine if receptor alterations exist in a peripheral tissue. The dissociation constant (Kd) of glucocorticoid receptors in the anterior pituitary of obese rats was 50% greater than the Kd of receptors derived from lean rats. This suggests a decrease in the affinity of these receptors and could indicate a reduced feedback inhibition of corticosterone at the anterior pituitary. Hepatic glucocorticoid receptors of obese rats also showed an increase (150%) in the Kd of binding and a reduction (40%) in the number of receptors. No difference was observed in the Kd or maximal binding of receptors from the hypothalamus or hippocampus of lean and obese rats. It appears that glucocorticoid receptor alterations exist in obese Zucker rats and that these alterations may affect the drive of the pituitary-adrenal axis and possibly the expression of obesity.

Animals↗
PubMed1990

Reflex and chemical responses of tracheal submucosal glands in piglets.

In adult animals, airway fluid secretion is enhanced reflexly via central nervous system pathways, and locally by mediators such as substance P. To evaluate the role of maturation on these regulatory mechanisms, we compared the effects of reflex stimulation and intravenous substance P administration on airway secretion in anesthetized, paralyzed and artificially ventilated piglets, 9 to 22 days of age, and older piglets all aged 10 weeks. Airway secretion was monitored by counting the hillocks appearing in the upper trachea in an exposed field of tracheal epithelium (1.2 cm2) coated with powdered tantalum. In younger animals, mechanical stimulation of the larynx had no discernible effect on tracheal submucosal gland secretion. Neither excitation of airway irritant receptors nor stimulation of pulmonary C-fiber receptors by capsaicin caused a significant increase of fluid secretion from tracheal submucosal glands. In addition, stimulation of peripheral chemoreceptors by ventilating animals with 12% O2 in N2, and 6% O2 in N2, failed to induce a substantial change in airway secretion, when compared with number of hillocks in the control period. Furthermore, administration of sodium cyanide had little or no effect on baseline secretion. In contrast, to the weak reflex responses in younger piglets electrical stimulation of the vagus nerve caused the number of hillocks to increase on average by 16.3 +/- 2.3 (P less than 0.01). In addition, local application of a pledget soaked in solution of methacholine caused the number of hillocks to increase by 32.1 +/- 5.2 (P less than 0.01). Intravenous administration of substance P also induced an augmentation in fluid secretion. Increase in concentration of substance P (10(-8), 10(-7), 10(-6), and 10(-5) M, 1 ml) was associated with a concomitant elevation in the number of activated submucosal glands (5.3 +/- 2.6, 10.0 +/- 4.4, 27.1 +/- 4.5, 41 +/- 5). In older piglets, stimulation of laryngeal mucosa, airway irritant receptors, as well as stimulation of pulmonary C-fiber receptors induced a significant increase in tracheal secretion, although stimulation of peripheral chemoreceptors had no effect on airway secretion. These data suggest that reflex responses of submucosal glands are weak during early postnatal development, however, tracheal submucosal glands do respond to exogenously administered cholinergic substances and tachykinin peptides.

Animals↗
PubMed1990

Continuous sucrose feeding decreases pain threshold and increases morphine potency.

Although an opioid-mediated mechanism appears to be involved in the alteration of pain perception during feeding behavior, little is known about macronutrient effects on nociception. In this report we show that prolonged sucrose feeding alters responsiveness to painful stimuli and the analgesic potency of morphine. Male Sprague-Dawley rats maintained on ad lib laboratory chow with continuous access to a 20% sucrose solution displayed a significant decrease in tail-flick latency as early as 20 hours after introduction of the sucrose. The differences in pain threshold were naloxone sensitive. After 25 days on the diet, morphine sulfate, 8 mg/kg administered IP, proved to be significantly more potent in the sucrose-fed animals. The results indicate that sucrose feeding alters endogenous opioid-mediated nociception.

Animals↗
PubMed1990

Adrenalectomy decreases neuropeptide Y mRNA levels in the arcuate nucleus.

Recent studies suggest that glucocorticoids may increase NPY and NPY mRNA levels. To determine if endogenous corticosterone affects the level of NPY mRNA in areas that control NPY levels in the paraventricular nucleus, we examined the effects of adrenalectomy and corticosterone replacement on NPY mRNA levels in the arcuate nucleus and brainstem. Rats were either adrenalectomized, adrenalectomized and corticosterone replaced, or sham-operated. The arcuate nucleus, hypothalamus (excluding arcuate nucleus), and brainstem were collected and the RNA isolated. Dot blots were made of each tissue and the NPY mRNA quantitated by densitometry. Adrenalectomy significantly reduced NPY mRNA levels in the arcuate nucleus, while corticosterone replacement restored the NPY mRNA levels. NPY mRNA levels in the remainder of the hypothalamus were not affected by adrenalectomy. Adrenalectomy also had no affect on NPY mRNA levels in the brainstem. These data suggest that the paraventricular nucleus may be affected by glucocorticoids via an NPY pathway and that the two major afferent pathways of NPY-containing neurons to the paraventricular nucleus may be regulated by different mechanisms.

Adrenal Glands↗
PubMed1990

Discontinuation of sustained sucrose-feeding aggravates morphine withdrawal.

Sprague-Dawley rats were allowed ad lib access to a 20% sucrose solution in addition to their normal diet to investigate the relationship between the prolonged consumption of a high carbohydrate diet and opioid function as evidenced by opioid dependence and withdrawal. Morphine dependence, assayed by tailflick, was induced, followed by naloxone-precipitated withdrawal, gauged by weight loss. Sucrose-fed animals developed lowered pain thresholds prior to dependence induction relative to those of control animals, but failed to exhibit any differences from controls in the development of dependence. Weight loss during withdrawal was increased by the discontinuation of sustained sucrose-feeding. In addition, the induction of dependence first decreased, then increased the animals' preference for sucrose. It is concluded that changes in opioid function caused by sustained sucrose-feeding are insufficient to affect the development of tolerance to morphine analgesia, but do aggravate the symptoms of precipitated withdrawal when access to sucrose is denied prior to the injection of naloxone.

Animals↗
PubMed1990

Early randomized intervention with high-frequency jet ventilation in respiratory distress syndrome.

To determine whether early use of high-frequency jet ventilation reduces neonatal mortality or pulmonary morbidity rates, we randomly selected 42 infants with clinical and radiographic evidence of severe respiratory distress syndrome to receive either high-frequency jet ventilation or conventional ventilation. Separate sequential analyses (two-sided, alpha = 0.05, power = 0.95 to detect 85:15 advantage) were performed for mortality rates, air leaks, bronchopulmonary dysplasia, intraventricular hemorrhage, and assignment crossover, and a combined analysis was performed, with death overriding other outcome variables. Enrollment was completed when the combined analysis reached the sequential design boundary indicating no treatment difference. Mortality rates (19% among infants receiving high-frequency jet ventilation vs 24% among infants receiving conventional ventilation), the incidence of air leaks (48% vs 52%), bronchopulmonary dysplasia (39% vs 41%), and intraventricular hemorrhage (33% vs 43%), and assignment crossovers (14% vs 24%) did not differs significantly between the treatment groups. We conclude that early use of high-frequency jet ventilation does not prevent or substantially reduce mortality or morbidity rates associated with assisted ventilation.

Age Factors↗
PubMed1990

The sleep-related worsening of lower airways obstruction: understanding and intervention.

The area of circadian rhythms and sleep altering lung function is relatively new to medicine. It is important to understand these changes to prevent complications from disease processes and to deliver the appropriate therapy over the entire day. This article focuses on the alterations during sleep in patients with lower airways obstruction. Asthma and chronic obstructive pulmonary disease are used as examples. Clinical and physiologic changes are discussed as well as treatment modalities.

Asthma↗
PubMed1990

Macronutrient selection in rats: effect of fat type and level.

The effect of type and level of dietary fat on subsequent diet selection was examined in young Sprague-Dawley rats. Isoenergetic, isonitrogenous diets composed of corn oil or tallow (commercial grade), each at 5 or 34%, were fed to rats for 2 wk, and their preference for diets covarying in carbohydrate and protein was subsequently tested. When compared to either of the corn oil groups or the 5% tallow group, rats previously fed the high tallow diet selected more protein and less carbohydrate. Subsequent experiments testing the effects of 5, 20 or 34% tallow indicated that this preference for protein was induced by exposure to the tallow diets for only 18 h. In addition, the 34% tallow group selected more protein than did rats fed 5 or 20% tallow. Tests of diet selection with 5 or 34% corn oil, tallow or hydrogenated coconut oil indicated that rats fed 34% tallow ate significantly more protein than the 34% corn oil group. Furthermore, animals fed a 34% pure, additive-free tallow diet exhibited a preference for protein. These studies suggest that the type and level of dietary fat interact to influence dietary selection.

Animals↗
PubMed1990

Effect of liver denervation on compensatory changes in food intake, body composition and hepatic enzyme induction after food restriction in rats.

The mechanisms involved in the recovery of body fat and liver metabolism after food restriction and refeeding are not understood. This study's aim was to determine the need for hepatic neural input for the compensatory changes in food intake, body composition and hepatic lipogenic enzymes seen upon realimentation after energy restriction. Rats underwent total surgical hepatic denervation or had sham operations. One group of sham-operated and denervated rats was fed a semipurified diet ad libitum; a second group was restricted to 40% ad libitum levels for 7 d, then given free access to food during a 2-d refeeding period. Body fat content and body fat recovery rate from below "set point" were not altered by hepatic denervation. These observations do not rule out liver involvement because blood-borne factors communicating energy status information to the central nervous system could be released from the liver. The activities of hepatic enzymes--glucose-6-phosphate dehydrogenase, malic enzyme and citrate cleavage enzyme--were stimulated at least twofold by restriction and refeeding when compared to ad libitum feeding. Hepatic denervation had no effect on basal enzyme levels in ad libitum-fed animals or on elevated enzyme activity induced by refeeding after food restriction. This study clearly demonstrates that hepatic innervation is not essential for energy balance and body composition regulation. The induction of lipogenic enzymes by food restriction and refeeding does not depend on central nervous system input to the liver.

ATP Citrate (pro-S)-Lyase↗
PubMed1990

Influence of serum glucose on glutamate decarboxylase activity in the ventromedial nucleus of rats.

Changes in the activity of glutamate decarboxylase (GAD), the rate-limiting enzyme in gamma-aminobutyric acid synthesis, in response to insulin-induced hypoglycemia were measured in several brain areas involved in glucoregulation. A 20% increase in GAD activity in the ventromedial nucleus (VMN) of rats was measured 30 min after injections of insulin. The increase was significantly correlated with the decrease in serum glucose (r = -0.74) and increased food intake (r = 0.44). The increase in VMN GAD activity was linear between 5 and 30 min after insulin injection and coincided with the decline in serum glucose. Pretreatment with a gastric preload of a 50% glucose solution attenuated the decline in serum glucose, the increase in food intake, and the increase in GAD activity. Inhibition of protein synthesis by puromycin did not block the decrease in glucose, but neither the increase in GAD activity in the VMN nor the increase in food intake in response to insulin was observed. The increase in VMN GAD activity also was present 6 h after insulin injection if rats were denied access to food. No consistent changes in GAD activity were measured in any brain area other than the VMN. The results of these trials suggest that the increase in VMN GAD activity is associated with the decrease in serum glucose and may be involved in the increased feeding associated with insulin administration.

Animals↗
PubMed1990

Site of action of putative lipostatic factor: food intake and peripheral pentose shunt activity.

Obesity due to overfeeding in one parabiotic rat results in mild hypophagia and specific loss of fat from its partner. Studies were conducted to determine whether the changes in body composition were reversible and whether the nonsignificant reduction in food intake was a primary response to a humoral lipostatic factor. Tube feeding partners of overfed rats 0.5 g more food per day than eaten voluntarily prevented loss of fat, although hepatic and adipose glucose-6-phosphate dehydrogenase activities were depressed. Glucose flux through the pentose phosphate pathway was inhibited in both adipose and hepatic tissue from thin partners of obese rats, although fatty acid synthesis was depressed only in adipose tissue. Response to insulin by adipocytes from ad libitum partners of obese rats appeared to be blunted, but insulin sensitivity was normal. When overfeeding stopped, both partners returned to control body composition, suggesting that the changes observed in parabiotic partners of obese rats were physiological responses to a putative circulating lipostatic factor rather than a nonspecific consequence of parabiosis.

Animals↗
PubMed1990

Effects of nasal CPAP on supraglottic and total pulmonary resistance in preterm infants.

The effects of continuous positive airway pressure (CPAP) on supraglottic and total pulmonary resistance were determined in 10 healthy premature infants (postconceptional age 34 +/- 2 wk, weight at study 1,628 +/- 250 g). Nasal airflow was measured with a mask pneumotachograph, and pressures in the esophagus and oropharynx were measured with a 5-Fr Millar or fluid-filled catheter. Nasal CPAP between 0 and 5 cmH2O correlated well with oropharyngeal pressure (r = 0.94). Total supraglottic resistance, total pulmonary resistance, and supraglottic resistance in inspiration and expiration were measured on increasing CPAP. Total supraglottic resistance decreased from 46 +/- 29 to 17 +/- 16 cmH2O.l-1.s (P less than 0.005) between 0 and 5 cmH2O CPAP, and a delay in return of resistance to control values was seen as CPAP was reciprocally decreased to 0. CPAP produced a decrease in supraglottic resistance in both inspiration and expiration, from 41 +/- 26 to 14 +/- 9 and from 33 +/- 17 to 10 +/- 6 cmH2O.l-1.s, respectively (P less than 0.01). Total pulmonary resistance also decreased from 161 +/- 40 to 95 +/- 24 cmH2O.l-1.s (P less than 0.01) between 0 and 5 cmH2O CPAP. The decrease in total supraglottic resistance in these infants accounted for 60% of the change in total pulmonary resistance, which occurred on CPAP of 5 cmH2O. We speculate that CPAP may decrease supraglottic resistance directly through mechanical splinting of the airway. This effect of CPAP may be the primary mechanism by which this form of therapy reduces apnea with an obstructive component in premature infants.

Airway Resistance↗
PubMed1990

Upper airway muscle and diaphragm responses to hypoxia in the piglet.

The neonatal ventilatory response to hypoxia is characterized by initial transient stimulation and subsequent respiratory depression. It is unknown, however, whether this response is also exhibited by the upper airway muscles that regulate nasal, laryngeal, and pharyngeal patency. We therefore compared electromyogram (EMG) amplitudes and minute EMGs for the diaphragm (DIA), alae nasi (AN), posterior cricoarytenoid (PCA), and genioglossus (GG) muscles in 12 anesthetized spontaneously breathing piglets during inhalation of 12% O2 over 10 min. Minute EMG for the DIA responded to hypoxia with an initial transient increase and subsequent return to prehypoxia levels by 10 min. Hypoxia also stimulated all three upper airway muscles. In contrast to the DIA EMG, however, AN, PCA, and GG EMGs all remained significantly above prehypoxia levels after 10 min of hypoxia. We have thus demonstrated that the initial stimulation and subsequent depression of the DIA EMG after 12% O2 inhalation contrast with the sustained increase in AN, PCA, and GG EMGs during hypoxia. We speculate that 1) central inhibition during neonatal hypoxia is primarily distributed to the motoneuron pools regulating DIA activation and 2) peripheral chemoreceptor stimulation and/or central disinhibition induced by hypoxia preferentially influence those motoneuron pools that regulate upper airway muscle activation, causing the different hypoxic responses of these muscle groups in the young piglet.

Animals↗
PubMed1990

Influence of sleep on lung volume in asthmatic patients and normal subjects.

To assess the effect of sleep on functional residual capacity (FRC) in normal subjects and asthmatic patients, 10 adult subjects (5 asthmatic patients with nocturnal worsening, 5 normal controls) were monitored overnight in a horizontal volume-displacement body plethysmograph. With the use of a single inspiratory occlusion technique, we determined that when supine and awake, asthmatic patients were hyperinflated relative to normal controls (FRC = 3.46 +/- 0.18 and 2.95 +/- 0.13 liters, respectively; P less than 0.05). During sleep FRC decreased in both groups, but the decrease was significantly greater in asthmatic patients such that during rapid-eye-movement (REM) sleep FRC was equivalent between the asthmatic and normal groups (FRC = 2.46 +/- 0.23 and 2.45 +/- 0.09 liters, respectively). Specific pulmonary conductance decreased progressively and significantly in the asthmatic patients during the night, falling from 0.047 +/- 0.007 to 0.018 +/- 0.002 cmH2O-1.s-1 (P less than 0.01). There was a significant linear relationship through the night between FRC and pulmonary conductance in only two of the five asthmatic patients (r = 0.55 and 0.65, respectively). We conclude that 1) FRC falls during sleep in both normal subjects and asthmatic patients, 2) the hyperinflation observed in awake asthmatic patients is diminished during non-REM sleep and eliminated during REM sleep, and 3) sleep-associated reductions in FRC may contribute to but do not account for all the nocturnal increase in airflow resistance observed in asthmatic patients with nocturnal worsening.

Adult↗
PubMed1990

Effect of sleep and sleep deprivation on ventilatory response to bronchoconstriction.

To characterize ventilatory responses to bronchoconstriction during sleep and to assess the effect of prior sleep deprivation on ventilatory and arousal responses to bronchoconstriction, bronchoconstriction was induced in eight asthmatic subjects while they were awake, during normal sleep, and during sleep after a 36-h period of sleep deprivation. Each subject was bronchoconstricted with increasing concentrations of aerosolized methacholine while ventilatory patterns and lower airway resistance (Rla) were continually monitored. The asthmatic patients maintained their minute ventilation as Rla increased under all conditions, demonstrating a stable tidal volume with a mild increase in respiratory frequency. Inspiratory drive, as measured by occlusion pressure (P0.1), increased progressively and significantly as Rla increased under all conditions (slopes of P0.1 vs. Rla = 0.249, 0.112, and 0.154 for awake, normal sleep, and sleep after sleep deprivation, respectively, P less than 0.0006). Chemostimuli did not appear to contribute significantly to the observed increases in P0.1. Prior sleep deprivation had no effect on ventilatory and P0.1 responses to bronchoconstriction but did significantly raise the arousal threshold to induced bronchoconstriction. We conclude that ventilatory responses to bronchoconstriction, unlike extrinsic loading, are not imparied by the presence of sleep, nor are they chemically mediated. However, prior sleep deprivation does increase the subsequent arousal threshold.

Adult↗
PubMed1990

Ventrolateral and dorsolateral ascending spinal cord pathway influence on thalamic nociception in cat.

1. In cat there are two portions of the spinothalamic tract (STT)--a ventral component, the ventral spinothalamic tract (VSTT) made up of axons of cells of spinal cord laminae IV-X, and a dorsolateral component, the dorsolateral spinothalamic tract (DSTT) made up of axons of cells in lamina I of the spinal cord dorsal horn. This study was designed to evaluate thalamic neuronal responses to cutaneous noxious thermal stimuli and to determine the functional importance of pathways ascending in the ventral and dorsolateral portions of the spinal cord, ipsilateral to the thalamic recording site and contralateral to the hindlimb stimulation region, for transmission of nociceptive information to the thalamus. 2. Extracellular single-unit recordings were made from 45 neurons in the ventrobasal complex (VBX) of cat thalamus. Thirty-five of these units responded either exclusively or preferentially to noxious cutaneous stimuli. Responses to noxious thermal stimuli applied to the unit's receptive fields were obtained, and then the effects on these responses of blocking conduction through the dorsolateral funiculus (DLF) and the ventrolateral quadrant (VQ) of the thoracic spinal cord ipsilateral to the thalamic recording site were determined. DLF and VQ conduction blocks were accomplished with the use of a cold probe technique and, at times, surgical lesions of the appropriate portion of the spinal cord. 3. The nociceptive units were located in the periphery of the ventral posterior lateral nucleus (VPL) of the thalamus. Their locations corresponded to the somatotopic organization of VPL. Nociceptive thermal responses were found in both high-threshold (HT) (10 cells) and wide-dynamic-range (WDR) (22 cells) units. The receptive fields of these units were generally small and were located on the hindlimb contralateral to the recording site. The thermoreceptive units had thresholds between 44 and 48 degrees C and were able to code for stimulus intensity. 4. Nine of the 35 nociceptive units demonstrated a decrease in response and two units an increase in response to noxious cutaneous stimulation during DLF block ipsilateral to the recording site and contralateral to the cutaneous stimulation site, whereas four units demonstrated a decrease in response and one unit an increase in response to noxious thermal cutaneous stimulation during VQ block ipsilateral to the recording site and contralateral to the cutaneous stimulation site.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗