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Biomedical subjects

J G Collins

Publications and source records attributed to J G Collins.

At least 91 records · Page 5Linked to original sources
PubMed1990

Serotonergic mediation of spinal analgesia and its interaction with noradrenergic systems.

Serotonin was administered intrathecally onto cat spinal cords to evaluate the pharmacology by which it suppresses noxiously evoked activity of wide-dynamic-range (WDR) neurons in the spinal dorsal horn. Doses of 500, 1,000 and 2,000 micrograms serotonin produced significant suppression of the mean noxiously evoked activity of WDR neurons in the dorsal horn of the spinal cord (21, 44, and 69% at 30 min, respectively). The dose-dependent effects were partially reversed by the intravenous administration of the serotonin antagonist methysergide (1 or 2 mg). Intravenous administration of the alpha 2-adrenergic antagonist yohimbine (0.5 or 1.0 mg/kg) produced a significant antagonism of the effects of serotonin. In contrast to the effects of methysergide and yohimbine, intravenous administration of naloxone or the alpha 1-antagonist corynanthine had no effect upon the suppressive effects of serotonin. The combination of low-dose serotonin and low-dose clonidine produced a supraadditive effect (30% at 30 min). These data support the concept that noradrenergic systems, possibly through an alpha 2-adrenergic mechanism, are involved in the modulation of spinal WDR neurons by serotonin.

Anesthesia, Spinal↗
PubMed1990

The antinociceptive role of mu- and delta-opiate receptors and their interactions in the spinal dorsal horn of cats.

This study was undertaken to examine the antinociceptive roles of different subtypes of opiate receptors and their interactions at the level of the spinal cord. We recorded extracellularly the activity of the single wide dynamic range neurons evoked by noxious radiant heat (51 degrees C) in decerebrate, spinally transected cats. The separate intrathecal administration of DAGO selective mu-agonist, n = 28), morphine (less selective mu-agonist, n = 22), DPDPE (selective delta-agonist, n = 25), and DADL (less selective delta-agonist, n = 17) produced statistically significant suppression of noxiously evoked activity in a time- and dose-dependent manner. In addition, intravenously administered naloxone (nonselective opiate antagonist) reversed the suppressive effects of all opiates studied. Intravenously administered ICI 174,864 (selective delta-antagonist) reversed the effects of DPDPE. These results, based on relative selectivity for opiate receptors, indicate that both mu- and delta-opiate receptors can modulate the input of nociceptive information in the spinal dorsal horn. To study interactions between mu- and delta-receptors at the level of the spinal cord, a combination of the above agonists was injected intrathecally--namely, an ineffective or slightly effective dose of DAGO (1 or 1.5 micrograms, respectively) that was combined with an ineffective dose of DPDPE (30 micrograms). The intrathecal combination of DAGO and DPDPE produced significant synergistic suppressive effects of noxiously evoked activity. These findings, again based on relative selectivity, suggest that drug combinations that include both selective mu- and delta-agonists may be a useful method of lowering the total amount of any one drug, thus decreasing the likelihood of side effects, while at the same time producing significant analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics, Opioid↗
PubMed1990

Enflurane depresses activity of the medullary inspiratory neurons in the cat.

The effect of enflurane on the firing activity (spikes/sec) of the inspiratory neurons of the dorsal respiratory group (DRG) of the medulla oblongata was studied in decerebrate, paralyzed, mechanically ventilated cats before and after bilateral cervical vagotomy. Inspiratory neuronal activity, phrenic neurogram, arterial blood pressure, tracheal pressure, and end tidal CO2 concentration were recorded. Cells whose firing activity was in phase with that of the phrenic nerve were considered inspiratory neurons. Administration of 1 and 2% enflurane in oxygen produced gradual, significant, and dose-dependent depression of the cell activity with cervical vagi either intact or severed. Recovery of the cell activity occurred after termination of enflurane administration. In cats with intact vagi, 10 min after introduction of 1 and 2% enflurane, the cell activity (mean +/- SE) expressed as percentage of the control was 70 +/- 6% (P less than 0.05) and 48 +/- 5% (P less than 0.01), respectively. Bilateral cervical vagotomy did not affect the degree of cell depression due to enflurane. Hypercarbia induced by inhalation of 5% CO2 increased cell activity, but it did not block enflurane-induced cell depression, although it reduced it. It may be concluded that enflurane depresses the activity of the inspiratory neurons of the DRG. The results also suggest that the respiratory depressant effect of enflurane has a central component and that the DRG region may serve as a site to mediate the enflurane-induced respiratory depression.

Animals↗
PubMed1990

Pentose phosphate pathway in rat colonic epithelium.

The colonic cells of the large intestine are one of the most proliferative tissues of the animal body. The pentose pathway has an essential role in cell division and growth being the only pathway forming ribose 5-P necessary for all nucleotide and nucleic acid sunthesis. The pentose pathway may also provide reducing potential as NADPH for biosynthesis and C-3- C-8 glycolyl compounds. The maximum catalytic capacities of the reactions of the non-oxidative pentose pathway for the conversion of ribose 5-P to hexose and triose phosphates by the proximal and distal colon under feeding and starvation regimes are among the highest in the animal body. The qualitative presence of the oxidative pentose pathway was assessed by measurement of the C-1/C-6 ratio value of 1.67-1.82. Enzymes of the F-type and L-type pentose pathways are present in colonocytes and their maximum catalytic activities in colonocyte cytosol are reported. The contribution of the F-type pentose cycle to the total glucose metabolism of colonocytes, measured by the specific yield method, is negligibly low (approximately 1.5%). Colonic epithelial cells use glucose at a high rate (7.1 +/- 0.33 mumol min-1g-1 dry wt) and 79% of the glucose is converted to lactate. Arabinose 5-P has an intermediary role in the formation of keto pentose, sedoheptulose and hexose phosphates from ribose 5-P by colonocyte cytosol. The intermediary and reaction products of [1-13C] ribose 5-P dissimilation by colonocytes is investigated by 13C NMR spectroscopy. The 13C positional isotope distributions show labelling of C-1 and C-3 of hexose 6-phosphates consistent with either the theoretical predictions of the F-type pentose pathway or of the activities of exchange reactions catalysed by transketolase and/or transaldolase. Measurements of exchange reactions showed that the C-1/C-3 labelling of these compounds is mostly, if not wholly, attributable to exchange catalysis by these group transferring enzymes. The results suggest that the F-type PC has little role in the glucose metabolism of colonocytes and pentose phosphate formation may thus occur by a contribution (approx 20% of the total glucose metabolism) by the alternate L-type pathway.

Animals↗
PubMed1990

Computer simulation of the pentose-phosphate pathway and associated metabolism used in conjunction with NMR experimental data from human erythrocytes.

A computer-based model of the metabolism of sugar phosphates by human erythrocytes has been developed to assist in the understanding of the biochemical transformations occurring in the pentose phosphate pathway. These transformations are reflected in the changes, with time, of the relative intensities of the metabolite peaks apparent in 1H, 13C and 31P NMR spectra. The deterministic model consists of 79 reactions interconnected in a defined structure and characterized by 155 rate constants. It also includes 17 different enzymes, 69 enzyme forms, 32 metabolites, and initial value of time and concentration of each of the reactants. The differential equations describing the time-dependence of the concentrations of the reactants are generated and then solved by using the computer program BIOSSIM, which is designed to solve arrays of "stiff" differential equations. We synthesized [1-13C]D-ribose 5-phosphate and used 13C and 31P NMR to monitor its transformation into various intermediates of the pentose phosphate pathway, after the addition of diluted haemolysates which had previously been depleted of nicotinamide- and adenine-nucleotides. The concentrations of several of the reactants were able to be quantified, while other peaks in both the 13C and 31P spectra are yet to be assigned with confidence. There was reasonable qualitative agreement between some aspects of the computer simulation of the proposed metabolic system and the experimental data.

Biotransformation↗
PubMed1990

[Effects of lactation on pregnancy induced analgesia during the postpartum period in rats].

Activation of an endogenous opioid system has been associated with an elevation in pain threshold during late pregnancy and the early postpartum period in rats. It is well established that endogenous opiates are involved in the physiological regulation on prolactin secretion. This study examined the influence of lactation on pregnancy-induced analgesia during the early postpartum period in rats. Three tests (colorectal distension, tail-flick and hot-plate) were used to assess each animal's response to painful stimuli. After determining pregnant baseline values, one group of rats (lactating, n = 21) were mated and retested on Day 7 and 21 of gestation and 1, 3, 5, 7 and 14 days after parturition. A non-lactating group of animals (n = 14) whose pups were removed immediately after delivery was tested in the same manner. On Day 21 of gestation significantly higher thresholds and longer latencies were observed. On Day 1 and 3 in both lactating and non-lactating rats, the values were still elevated. No significant difference was observed during the early postpartum period between the two groups. This study confirms the existence, in rats, of pregnancy-induced analgesia late in pregnancy and the early postpartum period. The analgesia during the early postpartum period is not influenced by lactation.

Animals↗
PubMed1990

Types of injuries by selected characteristics.

Estimates of the number of injuries, by type of injury, are presented by age, sex, race, geographic region, place of residence, class of accident, place of accident, and other socioeconomic and health variables. The numbers of days of restricted activity and bed disability due to injuries, by sex and type of injury, are also included.

Accidents↗
PubMed1989

Effects of solute conditions on the relative affinities of the oligonucleotides d(G-C)5 and d(A-T)5 for the anthracycline drug 2-fluoro-4-demethoxydaunomycin.

19F NMR has been used to show that changes in NaCl concentration, as well as the presence of lysine or arginine, affect the equilibrium distribution of the synthetic anthracycline 2-fluoro-4-demethoxydaunomycin (2FD) between binding sites on d(G-C)5 and d(A-T)5 in a 1:1:1 molar aqueous system: 2FD/d(G-C)5/d(A-T)5. Varying the pH between 6.2 and 7.7 had no effect. NaCl concentrations below 0.1 M led to a d(G-C)5 preference while above 0.1 M a preference for d(A-T)5 was observed. At comparable solute concentrations, use of either lysine or arginine resulted in a significant drug preference for d(G-C)5 compared to systems containing only NaCl.

Arginine↗
PubMed1989

A 19F-NMR study of 2-fluoro-4-demethoxydaunomycin intercalation complexes with the decanucleotides d(G-C)5 and d(A-T)5.

Binding configurations and equilibria of intercalation complexes formed by the novel anthracycline drug, 2-fluoro-4-demethoxydaunomycin (2FD), with the decanucleotides d(G-C)5 and d(A-T)5 have been studied by 19F-NMR spectroscopy. The 19F chemical shift of 2FD bound to d(A-T)5 was approximately 1.5 ppm downfield of that observed for 2FD bound to d(G-C)5. By mixing equimolar amounts of aqueous d(G-C)5, d(A-T)5 and 2FD, the distribution of drug between the nucleotides was followed by observing relative peak intensities and showed no G-C or A-T binding preference at room temperature. It was shown that each decanucleotide duplex bound three 2FD molecules, giving a neighbour exclusion parameter, n, of n = 3 for this drug. The stoichiometric complexes, which we denote by [d(A-T)5][2FD]3 and [d(G-C)5][2FD]3, were also purified and isolated in this study.

Daunorubicin↗
PubMed1989

Disruption of the rhythmic activity of the medullary inspiratory neurons and phrenic nerve by fentanyl and reversal with nalbuphine.

The effects of intravenous administration of fentanyl (50 and 100 micrograms/kg) on the discharge activity of the medullary inspiratory neurons and of the phrenic nerve were studied following vagotomy in nine decerebrate, paralyzed mechanically ventilated cats. In six cats, the inspiratory neurons explored were in the dorsal respiratory group (DRG) associated with the nucleus of the tractus solitarius (NTS), while in the remaining three, they were in the ventral respiratory group (VRG). In the former group, the rhythmic discharge of the inspiratory neurons was disrupted by fentanyl and replaced by a continuous discharge superimposed with irregularly occurring bursts. These changes were also reflected by the phrenic nerve discharge. Inspiratory neuronal activity increased significantly (P less than 0.05) at 1 and 5 min after completion of fentanyl injection. Disruption of the rhythmic activity of the inspiratory neurons and its replacement by a continuous and irregular discharge may lead to sustained contraction of inspiratory muscles and cessation of respiration. In the VRG, the activity of the inspiratory neurons was totally abolished by fentanyl. Thus, it appears that different groups of medullary inspiratory neurons have differential sensitivity to fentanyl. Nalbuphine, an opiate agonist-antagonist, restored the normal pattern and magnitude of the activity of the inspiratory neurons.

Animals↗
PubMed1989

Non-invasive intravital fluorescent microscopy of the hamster gingiva.

Several attempts have been made to visualize the gingival microcirculation of small animals. Most of these attempts have required surgical procedures without control of the local tissue environment. In our current study of the hamster gingiva, a tissue bath was designed to allow microcirculatory observations of the periodontium of the superior incisors without the need for invasive surgical procedures and with controlled pH and temperature of the bathing solution. Dextrans (m.w. = 70,000 and m.w. = 150,000), bovine serum albumin (mw = 66,210) or a globulin fraction (mw = greater than 450,000 less than 825,000) were conjugated to fluorescein isothiocyanate and injected into the animal. Fluorescent images, produced by epi-illumination, were analyzed for the light intensity of the interstitium. There was a large and rapid increase in light intensity (leakage of the macromolecules) near the venules while capillaries of the gingival margin developed interstitial fluorescence at a slower rate and with a lower maximal effect. Molecular weight, shape or charge of the macromolecular or age of the animal did not affect the results. This new preparation could be used to study the contribution of the microcirculation to gingivitis, the role of gingivitis in the development of periodontal disease, or the effects of drugs and hormones on the microcirculation of the gingiva.

Animals↗
PubMed1989

Trends in COPD morbidity and mortality in the United States.

This paper describes patterns and trends in COPD morbidity and mortality based on data from several data systems of the National Center for Health Statistics (NCHS), as follows: mortality data from the National Vital Statistics System; and morbidity data from the National Health Interview Survey, the National Hospital Discharge Survey, and the National Ambulatory Medical Care Survey. The paper focuses on the period 1979 to 1985 and the age groups 55 years old and over. old and over. Data are also presented separately for men and women. In addition to presenting rates for prevalence, hospital discharges, office visits, and deaths on a population basis, the paper also presents rates and analyses on a per case basis, using a "pseudo-natural history model." This paper also describes some of the methodological issues associated with analyzing comparative data from several NCHS data systems.

Age Factors↗
PubMed1989

Intrathecal clonidine suppresses noxiously evoked activity of spinal wide dynamic range neurons in cats.

The analgesic effectiveness of perispinal clonidine administration prompted us to evaluate clonidine effects on spinal dorsal horn wide dynamic range neurons. Intrathecal clonidine produced a dose-dependent (10 and 30 micrograms), yohimbine-reversible suppression of noxiously evoked activity in decerebrate, spinal cord-transected cats. In addition, combining ineffective intrathecal doses of morphine (25 micrograms) and clonidine (5 micrograms) produced statistically significant, reversible suppression of noxiously evoked activity. The time course of suppression was similar to that observed behaviorally. These results support the role of spinal alpha 2-adrenergic receptors in clonidine analgesia.

Analgesics↗
PubMed1989

Spinal cord distribution of 3H-morphine after intrathecal administration: relationship to analgesia.

The distribution of intrathecally administered 3H-morphine was examined by light microscopic autoradiography in rat spinal cord and temporal changes in silver grain localization were compared with results obtained from simultaneous measurements of analgesia. After tissue processing, radio-activity was found to have penetrated in superficial as well as in deeper layers (Rexed lamina V, VII, and X) of rat spinal cord within minutes after application. Silver grain density reached maximal values at 30 min in every region of cord studied. Radioactivity decreased rapidly between 30 min and 2 hr and then more slowly over the next 24 hr. In rats tested for responses to a thermal stimulus (tail flick test), intrathecal administration of morphine (5 and 15 micrograms) resulted in significant dose dependent analgesia that peaked at 30 min and lasted up to 5 hr (P less than 0.5). There was a close relationship between analgesia and spinal cord silver grain density during the first 4 hr of the study. It is postulated that the onset of spinal morphine analgesia depends on appearance of molecules at sites of action followed by the activation of anti-nociceptive mechanisms.

Analgesia↗
PubMed1988

Fentanyl suppression of nociceptive neurons in the superficial dorsal horn of the cat.

This study was designed to examine the influence of spinally administered fentanyl on the spontaneous and noxiously evoked activity of high threshold (HT) and wide dynamic range (WDR) neurons in the superficial layers (lamina I and II) of the dorsal horn of cats made decerebrate and in which the spinal cord had been transected. Single unit activity was recorded using extracellular microelectrode recording techniques. Neuronal activity was evoked by the presentation of noxious radiant heat (51 degrees C) to the cells' receptive fields on the hind paws. Evoked activity of WDR neurons was monitored, both before and after the spinal administration of either 10 micrograms (n = 9) or 25 micrograms (n = 10) of fentanyl. HT neurons were examined before and after either 25 micrograms (n = 7) or 50 micrograms (n = 7) of spinally administered fentanyl. In all cases 31 min after fentanyl administration naloxone (0.1 mg) was administered intravenously (iv), and its antagonistic effect on the fentanyl suppression was determined. All doses of fentanyl tested suppressed both spontaneous and evoked activity of both types of neurons. Within 30 minutes 10 and 25 micrograms of fentanyl reduced the mean evoked activity of WDR neurons to 61% and 19% of control values, respectively, and 25 and 50 micrograms of fentanyl reduced the mean evoked activity of HT neurons to 70% and 47% of control values, respectively. Naloxone reversed the suppression seen in all cells studied. The results of the present study demonstrate that HT neurons are significantly less suppressed by the spinal administration of fentanyl than WDR neurons located in the same superficial layers of the dorsal horn.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗