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Biomedical subjects

R J Martin

Publications and source records attributed to R J Martin.

At least 199 records · Page 11Linked to original sources
PubMed1995

Comparison of daily versus continuous administration of somatotropin on growth rate, feed intake, and body composition in intact female rats.

The response to continuous delivery or daily bolus injection of porcine somatotropin (pST) was compared in mature, pituitary-intact female rats (225 g). Growth rate in control rats was approximately 1 g/d over the 14-d study. There was a dose-dependent (0, .4, 1.2, and 3.6 mg of pST/d; P < .001) increase in rate of gain with an interaction (P < .001) of dose and mode of delivery. The slope of the dose-response curve for growth rate was linear on a logarithmic scale for both modes of delivery but was greater for continuous delivery. At the low dose (.4 mg/d) pST stimulated gain (21.7 g/14 d above control, P < .05) when administered by daily injection but failed to stimulate gain (6.0 g/14 d above control, NS) when delivered continuously. At the high dose (3.6 mg/d), gain (above that in control rats) was 49.1 and 79.7 g/14 d for daily and continuous delivery; the two modes were different (P < .05) from each other. Feed intake and liver weights were also stimulated by pST in a dose-dependent manner. The increase in liver size was accompanied by a dose-dependent increase in liver DNA, indicative of an increase in cell number. Increased carcass gain was largely accounted for by increased carcass protein accretion. Rates of carcass lipid accretion were lower than those for protein accretion and were further decreased by pST, particularly by the high dose administered by continuous delivery, where a negative lipid accretion value was observed. Circulating IGF-I was increased by pST (P < .001) but was not affected by the mode of delivery. The results demonstrate that the increased gain observed in mature rats is largely due to lean tissue accretion and is accompanied by an increase in feed intake.

Animals↗
PubMed1995

Nocturnal asthma and exercise-induced bronchospasm. Why they occur and how they can be managed.

Asthma is increasing in prevalence and morbidity worldwide. Worsening of asthma symptoms during sleep and following exercise is an important component of this morbidity. Better recognition and management of nocturnal asthma and exercise-induced broncho-constriction should lead to improved outcomes. Measures to alleviate nocturnal asthma include elimination of exposure to allergens, use of measures to control contributing factors (rhinitis, sinusitis, gastroesophageal reflux, sleep apnea), maximization of the dosage of daytime asthma medications, and appropriately timed use of medications such as a long-acting inhaled beta 2 agonist, a once-daily sustained-release theophylline product, and an oral corticosteroid. Bronchoconstriction after exercise can be decreased by physical conditioning, warm-up exercises, wearing of a face mask in cold weather, postponement of exercise until at least 2 hours after a meal, and pretreatment with an inhaled beta agonist. Pretreatment with inhaled cromolyn sodium (Intal), nedocromil sodium (Tilade), or ipratropium bromide (Atrovent) may be added if necessary.

Asthma↗
PubMed1995

Chronobiology and chronotherapy of asthma.

There is no doubt that many pathophysiologic conditions change over a 24-hour period and thus therapy needs to be directed at these changes. In particular, asthma has been one of the better-studied disease processes in regard to circadian changes in pathophysiology. As we continue to learn more about circadian changes, better approaches to treating the disease with the same medications will emerge. It should be remembered that many asthmatics do not perceive their degree of bronchoconstriction. This was brought forth in Turner-Warwick's epidemiologic study in that less than one half of the asthmatic individuals who had problems with their asthma every night describe their asthma as being severe. The majority stated they either had mild or moderate asthma. Therefore, it is important that we use objective criteria such as peak flow meters in determining an individual patient's day-to-night changes in lung function. Then, any therapeutic intervention can be objectively determined at home with both the patient and physician gaining knowledge about the ongoing asthmatic process.

Asthma↗
PubMed1994

The action of pyrantel as an agonist and an open channel blocker at acetylcholine receptors in isolated Ascaris suum muscle vesicles.

The anthelmintic pyrantel is believed to act as an agonist at acetylcholine receptors on somatic muscle from the parasite Ascaris suum. This study aimed to confirm this mode of action of pyrantel. Single-channel recordings from muscle vesicles formed from the extrasynaptic region of the bag of somatic muscle cells of Ascaris suum were made using the patch-clamp technique. Pyrantel (0.03-100 microM) activated cation-selective channels with at least 2 conductance levels: main conductance 41 +/- 2.04 pS (mean +/- S.E., n = 28), smaller conductance 22.4 +/- 0.34 pS (mean +/- S.E., n = 8). The current/voltage plots showed a linear relationship. Detailed kinetic analysis revealed that activation of the receptor by pyrantel resulted in at least 2 distinct open and burst states and at least 3 distinct closed states. The mean open time of the channel, with 0.1 microM pyrantel, was 1.53 +/- 0.22 ms (mean +/- S.E., n = 7) at -75 mV. We have previously shown that acetylcholine activated channels with similar properties to the pyrantel-activated channels (Pennington, A.J. and R.J. Martin, 1990, J. Exp. Biol. 154, 201) confirming that pyrantel is an acetylcholine agonist. With high concentrations (100 microM) of pyrantel a sequence of rapid openings and closings of the channel was observed, indicating the presence of an open channel block. Previous experiments have shown that the anthelmintic levamisole, which also acts as an acetylcholine agonist on this preparation, induced channel block at hyperpolarised potentials with high concentrations (Robertson, S.J. and R.J. Martin, 1993, Br. J. Pharmacol. 108, 170). A comparison is made of the actions of the 3 agonists pyrantel, levamisole and acetylcholine at the nicotinic receptor in Ascaris muscle, and implications for the therapeutic use of the compounds are discussed.

Acetylcholine↗
PubMed1994

Differential expression of lymphocyte homing receptors by human memory/effector T cells in pulmonary versus cutaneous immune effector sites.

The heterogeneous expression of lymphocyte homing receptors (HR) by the (CD45RA(low)/RO(high)) memory/effector T cell population in the human is thought to define subsets with tissue-selective recirculatory potential. To investigate further the localization characteristics of these T cells, we used multiparameter flow cytometry to quantitate T cell subsets defined by expression of the skin-selective HR called the cutaneous lymphocyte-associated antigen (CLA), the peripheral lymph node (PLN) HR L-selectin, the mucosal-associated HR alpha 4 beta 7-integrin, and the mucosal-associated adhesion molecule alpha e beta 7-integrin in either cutaneous or pulmonary immune effector sites and corresponding peripheral blood. Compared to peripheral blood, skin T cells were highly enriched for the CLA+/L-selectin+/alpha e beta 7-integrin- memory/effector subset, whereas lung memory/effector T cells were predominantly CLA-to low L-selectin-, and almost half were alpha e beta 7-integrin+. alpha 4 beta 7-integrin expressing memory/effector T cells were diminished in both skin and lung, suggesting that this HR is not a major participant in determining localization specificity in either of these sites. The characteristic pulmonary T cell HR phenotype did not significantly differ between the normal subjects and those with pulmonary inflammatory disease, and did not correlate with markers of T cell activation. Induction of a rapid up-regulation of pulmonary inflammation via intrabronchial allergen challenge in asthmatic patients tended to decrease localization specificity, resulting in a more general importation of memory/effector subsets. Taken together, these results suggest that tissue microenvironments play a major role in determining the character of local T cell infiltrates via their ability to import and retain memory/effector subsets selectively or, more generally, depending on the intensity of local inflammatory stimuli.

Antibodies, Monoclonal↗
PubMed1994

Effects of a fat substitute, sucrose polyester, on food intake, body composition, and serum factors in lean and obese Zucker rats.

Sucrose polyester, a fat substitute, has shown promise in reducing blood cholesterol and body weight of obese individuals. Effects of this compound in the Zucker rat, a genetic model of obesity, are unknown. Thus, we examined food intake, body weight, body composition, and several metabolic parameters in sera of lean and obese female Zucker rats. Eight-week-old lean and obese animals were given a choice between a control diet (15% corn oil) and fat substitute diet (5% corn oil and 10% sucrose polyester) for 2 days. Next, one-half of the lean and obese groups received control diet; the remaining lean and obese rats received fat substitute diet for 18 days. Cumulative food intake was depressed in fat substitute groups relative to control-fed animals; however, this effect was more predominant in obese animals. Obese rats consuming fat substitute diet (O-FS) gained less weight as compared to obese control-fed animals (O-C). Lean rats given fat substitute (L-FS) did not have significantly different body weights as compared to the L-C group. Fat substitute groups, combined, had lower body fat and higher body water as compared to controls. The O-FS group had lower serum glucose and insulin and higher fatty acid levels compared to the O-C group. There were no differences in serum cholesterol, HDL, or triglyceride levels due to fat substitute diet. These data suggest that the obese Zucker rat is unable to defend its body weight when dietary fat is replaced with sucrose polyester.

Animals↗
PubMed1994

Endocrine regulation of fetal adipose tissue metabolism in the pig: role of hydrocortisone.

Glucocorticoids have been shown to be essential for the excessive fat deposition and development of obesity in several animal models. This study was performed to characterize the role of glucocorticoids in the developmental regulation of adipose tissue metabolism. On day 70 of gestation, pig fetuses were hypophysectomized by micro-cauterization. Hypophysectomized fetuses were implanted subcutaneously with hydrocortisone pellets or received no hormone replacement. Fetuses were removed by laparotomy on day 90 of gestation. Additional fetuses were hypophysectomized on day 70, implanted with hydrocortisone pellets on day 90 and removed on day 105 of gestation. Several intact fetuses were also implanted subcutaneously with hydrocortisone pellets during this later gestational period. Serum cortisol concentrations were reduced in hypophysectomized pigs at both fetal ages and were restored to intact levels by hydrocortisone treatment. Hydrocortisone supplementation enhanced lipolytic response to isoproterenol in intact fetuses but failed to restore lipolytic response to isoproterenol in hypophysectomized animals at either fetal age. Hydrocortisone induced a slight increase in lipogenesis in hypophysectomized fetuses when administered from 70 to 90 days of gestation and a more dramatic increase when administered from days 90 to 105 of gestation. However, hydrocortisone had no effect on basal or insulin stimulated lipogenesis in intact fetuses when administered from days 90 to 105 of gestation. These results indicate that hydrocortisone may have a primary influence on adipose tissue metabolism during late fetal development only in the absence of inhibition from counterregulatory hormones of pituitary origin.

Adipose Tissue↗
PubMed1994

Maturation of the cholinergic response of tracheal smooth muscle in the piglet.

Maturational changes of the contractile properties of airway smooth muscle have been suggested to occur during the late prenatal and early postnatal period in the piglet. However, the timing and mechanisms involved remain elusive. Therefore, we studied isometric contraction of tracheal smooth muscle (TSM) to evaluate the effects of maturation on 1) the response of TSM to the muscarinic agonist acetylcholine (Ach); and 2) the regulatory activity of acetylcholinesterase (AChE) during the early postnatal period in the piglet. Studies were performed in 1-5-day-old (n = 6) and 14-22-day-old (n = 8) anesthetized, mechanically ventilated piglets. Changes in tracheal tension were measured in vivo from an open tracheal segment and normalized for both longitudinal length of the tracheal segment and cross-sectional area. Dose-response curves to locally applied Ach were obtained before and after the intravenous administration of the AChE inhibitor physostigmine (Phys). Ach-induced changes in tracheal tension significantly increased with maturation during the first 3 weeks of life (P < 0.01), regardless of normalization method. The addition of Phys significantly increased the cholinergic responses of TSM in both age groups (P < 0.02). However, this increase was comparable between age groups. There was also no difference in AChE activity measured in tracheal smooth muscle homogenates between the 1-5 and 14-22-day-old animals. These data indicate that maturation significantly enhances the cholinergic responses of tracheal smooth muscle in the early postnatal period in the piglet.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

The Ca-activated chloride channel of Ascaris suum conducts volatile fatty acids produced by anaerobic respiration: a patch-clamp study.

Plasma membrane vesicles prepared from the bag region of the somatic muscle cell of the parasite Ascaris suum contain a large conductance, voltage-sensitive, calcium-activated chloride channel. The ability of this channel to conduct a variety of carboxylic acids, a number of which are products of anaerobic respiration, was investigated using the patch-clamp technique and isolated inside-out patches of muscle membrane. The channel has a conductance of 140 pS in symmetrical 140 mM chloride. Replacement of internal chloride with various carboxylic acids (140 mM) caused large hyperpolarizing shifts in the reversal potential. Permeability ratios, relative to chloride, were calculated for each acid. The relationship between permeability ratio and ionic size is inverse and linear predicting a pore diameter of 6.55 A. This simple relationship was not observed between ionic size and conductance. Calculation of the transition state energy required to transfer a single methyl group from aqueous phase to the binding site afforded a value that was low but favorable, indicating a cationic binding site of low field strength. As the channel is able to open fully at the resting membrane potential of Ascaris and is permeable to fatty acids produced by anaerobic respiration, the possible role of this channel in the removal of metabolic products across the muscle membrane is discussed.

Animals↗
PubMed1994

Effects of dietary fat on food intake and brain uptake and oxidation of fatty acids.

The present study was designed to investigate (a) whether dietary fat manipulation, quantitatively and/or qualitatively, may influence the transport of fatty acids into the brain and oxidation of fatty acids in the hypothalamus; and (b) if an inhibitor of fatty acid oxidation changed food intake on these diets. Rats were fed for 4 wk 5% or 34% corn oil or tallow diets that were isocaloric and isonitrogenous. It was found that rats fed corn oil diets had significantly higher brain uptake index of palmitate than did rats fed tallow diets. In a second experiment, rats were fed either 30% corn oil or tallow diets and injected with either saline or mercaptoacetate (MA). Both saturated fat diets and mercaptoacetate injection reduced lateral hypothalamic, but not ventromedial hypothalamic fatty acid oxidation. Mercaptoacetate increased food intake only in the corn oil fed rats. It is proposed that these uptake and metabolic changes contribute to alterations in either energy expenditure or feeding behavior.

Animals↗
PubMed1994

Hypoglossal and phrenic responses to central respiratory inhibition in piglets.

Neonatal apnea is characterized by decreased neural output to the ventilatory muscles, and frequently associated with upper airway obstruction. We sought to characterize: (1) the role of central chemosensitive structures at the ventral medullary surface (VMS) in modulating hypoglossal and phrenic neural output, and (2) the recovery of hypoglossal and phrenic neural output during simulated central apnea. We studied 14 anesthetized, paralyzed, ventilated piglets aged 14-21 days and performed VMS cooling to inhibit central neural pathways mediating CO2 sensitivity. Phrenic and hypoglossal ENGs and end-tidal CO2 were continuously recorded. During CO2 rebreathing, hypoglossal activity was always more sensitive than phrenic activity to the inhibitory effects of VMS cooling. When phrenic apnea was induced by VMS cooling, and followed by discontinuation of ventilation for 60 sec in order to induce simultaneous hypercapnia and hypoxia, reappearance of hypoglossal ENG was delayed and recovery was significantly suppressed when compared to phrenic ENG. Therefore, attenuated central chemosensitivity during early postnatal life appears to preferentially inhibit neural output responsible for upper airway patency, and may predispose to upper airway obstruction during recovery from neonatal apnea.

Animals↗
PubMed1994

Single oral dose of prednisone decreases leukotriene B4 production by alveolar macrophages from patients with nocturnal asthma but not control subjects: relationship to changes in cellular influx and FEV1.

BACKGROUND: Nocturnal worsening of asthma is associated with an increase in numbers of airway inflammatory cells during the early morning. However, cell function during the night, with and without administration of steroids, has not been investigated. OBJECTIVE: This study was designed to determine the effect of prednisone on pulmonary alveolar macrophage production of leukotriene B2 and thromboxane B2 at night and how it relates to changes in pulmonary function and cellular influx. METHODS: Alveolar macrophages were obtained from patients with nocturnal asthma, patients with nonnocturnal asthma, and normal control subjects at 4:00 AM by bronchoalveolar lavage after administration of placebo and prednisone. Cells were placed in limited cell culture, and eicosanoids were measured from baseline and stimulated cells. RESULTS: Patients with nocturnal asthma had both a significantly greater fall in forced expiratory volume in 1 second (FEV1) and a greater influx of neutrophils and eosinophils at 4:00 AM than normal subjects after placebo treatment, whereas patients with nonnocturnal asthma had intermediary responses. There was no difference in baseline or stimulated LTB4 production during placebo administration in the three groups. After prednisone treatment, there was an improvement in the nocturnal fall in FEV1 and a significant decrease in the neutrophil influx in patients with nocturnal asthma compared with the other groups. These changes were accompanied by a significant decrease in the stimulated LTB4 production in patients with nocturnal asthma compared with a small increase in both patients with nonnocturnal asthma and normal subjects. Thromboxane B2 production did not change. The decrease in LTB4 production was correlated with the fall in granulocytic cells and improvement in the nocturnal FEV1. However, the two variables with the greatest combined influence on the improvement in FEV1 were the decrease in stimulated LTB4 production and the fall in neutrophil influx. CONCLUSIONS: We demonstrate for the first time that a single oral dose of prednisone decreases LTB4 production from alveolar macrophages, obtained at night from patients with nocturnal asthma, during a time of known inflammation. Further, this decrease in stimulated production is associated with decreases in cellular influx and improvement in pulmonary function.

Administration, Oral↗
PubMed1994

Vagotomy and mercaptoacetate influence the effect of dietary fat on macronutrient selection by rats.

We have previously shown that rats fed saturated fat prefer a high protein, low carbohydrate diet, whereas animals fed unsaturated fat prefer a low protein, high carbohydrate diet. The purpose of the present study was to determine whether this "saturated fat effect" requires 1) the oxidation of the dietary fat and 2) an intact hepatic vagus nerve. Male Sprague-Dawley rats were vagotomized (hepatic branch) or sham-operated and injected with either mercaptoacetate (fatty acid oxidation inhibitor) or saline. Next, half of each group was given saturated fat (beef tallow) or unsaturated fat (corn oil) by gastric tube. All animals were given a choice between two mixed diets that differed in protein and carbohydrate. Sham-operated rats fed saturated fat ate more of the protein diet than did rats fed unsaturated fat. Vagotomy attenuated the intake of the protein diet in animals fed saturated fat. Mercaptoacetate or vagotomy had no effect on diet selection in rats fed unsaturated fat. These data indicate that the effect of saturated fat on diet selection requires an intact hepatic vagus and may be modulated by fatty acid oxidation. Furthermore, the mechanism for altering diet selection can be induced after a single meal.

3-Hydroxybutyric Acid↗
PubMed1994

Low protein diets increase neuropeptide Y gene expression in the basomedial hypothalamus of rats.

Food deprivation elevates both neuropeptide Y (NPY) gene expression in the basomedial hypothalamus and NPY levels in the paraventricular nucleus (PVN). To gain a better understanding of the dietary control of NPY, we systematically examined the effects of macronutrient restriction on the gene expression of NPY in the basomedial hypothalamus and NPY content in the PVN. Rats were fed one of eight different diets for 12 d. The control group was fed a modified AIN-76 diet. One group was fed the modified AIN-76 diet but was restricted in energy by 50%. Six isocaloric (to the control diet) test diets were prepared, each with an individual macronutrient reduced by 50%. Neuropeptide Y gene expression was elevated in protein-restricted animals as well as in energy-restricted animals. Carbohydrate or fat restriction seemed to have no effect on NPY gene expression. Though the NPY content in the PVN was not different between any groups, two findings were consistent with greater NPY release in protein-restricted animals. Animals fed a low protein diet were hyperphagic and had a greater amount of body fat. This study suggests that low levels of dietary protein may have a role in the regulation of NPY gene expression.

Animals↗
PubMed1994

Interaction of insulin and somatotropin on body weight gain, feed intake, and body composition in rats.

This study investigated the interaction of insulin and somatotropin on body weight gain and feed conversion in rats. Female rats (initial wt 215 g) were assigned to one of the following four treatments for a 2-wk period: 1) control; 2) 40 U protamine zinc insulin.kg-1.day-1; 3) 2 mg/day somatotropin; 4) insulin + somatotropin. Relative to the control group (gain, 1.4 g/day; intake, 16.7 g/day) insulin stimulated the rate of gain (250%), feed intake (73%), and fat pad weight (215%). Insulin caused a 270% increase in carcass fat and a 30% increase in carcass protein. Somatotropin also increased gain (178%) but did not have a significant effect on intake or fat pad weight. Somatotropin increased carcass protein 28% but had no effect on carcass fat. The greatest stimulation of body weight gain (392%) was observed with the insulin plus somatotropin combination treatment, indicating an additive effect. There were also additive effects on protein accretion and organ weights. However, feed intake and carcass fat in the combination group were intermediate between that of the control and insulin alone groups, indicating that somatotropin attenuated the ability of insulin to stimulate these parameters. These results indicate that certain effects of insulin and somatotropin, such as the promotion of lean tissue accretion, are additive, whereas other effects, such as those associated with lipid metabolism, oppose each other.

Adipose Tissue↗