Biomedical subjects

B Hoskins

Publications and source records attributed to B Hoskins.

At least 19 recordsLinked to original sources

PubMed1999

The effect of phosphate on the relaxation of frog skeletal muscle.

The effect of phosphate on the relaxation of isometrically contracting single skinned fibres from the semitendinosus muscle of the frog Rana temporaria has been investigated using laser pulse photolysis of the photolabile caged calcium-chelator diazo-2 to rapidly reduce the Ca2+ (<2 ms) within the fibre and produce >90% relaxation of force. Relaxation occurred in two phases - an initial linear shoulder which lasted approximately 20 ms followed by a double-exponential phase which gave two rate constants, k1 (43.4+/-1. 8 s-1, mean +/-SEM, n=14) and k2 (15.6+/-0.3 s-1, mean +/-SEM, n=14) at 12 degreesC. Increased phosphate concentrations did not affect the linear phase, but slowed the double-exponential phase following photolysis of diazo-2 in a dose-dependent fashion (k50= 0.9 mM for k1, 1.15 mM for k2). Reducing the concentration of contaminating phosphate (from 640 microM to 100 microM) led to an increase in the rate of the double-exponential phase (k1=67.1+/-4.4 s-1, k2=19.7+/-0. 6 s-1, mean +/-SEM, n=12). Time-resolved measurements of sarcomere length during relaxation, both in control fibres and in the presence of a raised phosphate concentration, reveal a <2% change throughout the whole relaxation transient, and less than 0.1% at the end of the linear phase. This finding implies that gross changes in sarcomere length do not contribute to the decay of the relaxation transient seen upon diazo-2 photolysis. Our results suggest that cross-bridges in states prior to phosphate release are already committed to force generation and must relax by releasing phosphate, rather than by a reversal of the force-generating step to a weakly bound, low-force phosphate-bound state. These findings also indicate that an increase in the phosphate concentration within muscle fibres plays an important part in the slowing of relaxation observed in skeletal muscle fatigue and that the relaxation transients observed upon diazo-2 photolysis represent a disengagement of the cross-bridges.

Adenosine Diphosphate↗

PubMed1997

Consumer reports in health care. Do they make a difference in patient care?

CONTEXT: Consumer reports in health care are a relatively recent phenomenon. Primarily designed to assist consumers in making more informed decisions about their personal health care, they appear to have an important by-product-they led to positive changes in the behavior of clinicians and health care delivery organizations. While there has been much speculation on their impact on health care consumer behavior, consumer reports offer an effective strategy in improving the quality of patient care. OBJECTIVE: To examine the impact of an obstetrics consumer report developed and issued by the Missouri Department of Health on hospital behavior. DESIGN AND SETTING: A retrospective study of hospital behavior using both primary survey and secondary clinical data. PARTICIPANTS: Consumer reports were issued in 1993 to all Missouri hospitals providing obstetrical services (n=90). A survey was conducted a year later, and the results were analyzed with other available data to determine the effect of the report. Two hospitals discontinued obstetrical services by the time of the survey; of the remaining 88 hospitals, 82 (93%) responded to the survey. MAIN OUTCOME MEASURES: The following outcomes were examined: (1) number and percentage of hospitals that previously did not have services at the time report was issued, but had, or planned to have, services after a guide was published; (2) the percentage of obstetrical policies that were changed, planned to change, or are under discussion for change (car seat program, obstetrical follow-up services, formal transfer agreement, nurse educator for breast-feeding, and availability of tubal ligations); and (3) clinical outcomes, including satisfaction, appropriateness of charges, and the rates of cesarean delivery, high-risk infant transfer, ultrasound, vaginal birth after cesarean, very low birth weight, and newborn death. RESULTS: Within 1 year of the report, approximately 50% of hospitals that did not have car seat programs, formal transfer agreements, or nurse educators for breast-feeding prior to the report either instituted or planned to institute these services. Hospitals in competitive markets that did not offer one of these services at the time of the report were more likely to institute a service and/or were about twice as likely to consider improving several indicators. Clinical outcome indicators all improved in the expected direction. CONCLUSION: Public release of consumer reports may be useful not only in assisting consumers to make informed health care choices, but also in facilitating improvement in the quality of hospital services offered and care provided. Changes occur especially in competitive markets.

Cesarean Section↗

PubMed1996

Naloxone-precipitated changes in biogenic amines and their metabolites in various brain regions of butorphanol-dependent rats.

Influence of a naloxone (an opioid receptor antagonist) challenge (5 mg/kg, IP) on levels of biogenic amines and their metabolites in various brain regions of rats infused continuously with butorphanol (a mu/delta/kappa mixed opioid receptor agonist; 26 nmol/microliter/h) or morphine (a mu-opioid receptor agonist; 26 nmol/microliter/h) was investigated using high-performance liquid chromatography with electrochemical detection (HPLC-ED). Naloxone precipitated a withdrawal syndrome and decreased the levels of: dopamine (DA) in the cortex and striatum, 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum, homovanilic acid (HVA) in the striatum, limbic, midbrain, and pons/medulla regions in butorphanol-dependent rats. However, the levels of norepinephrine (NE), serotonin (5-hydroxytryptamine; 5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the regions studied were not affected by naloxone-precipitated withdrawal. In addition, naloxone increased the HVA/DA ratio in the cortex, while this ratio was reduced in the limbic, midbrain, and pons/medulla. The reduction of 5-HIAA/5-HT ratio was also detected in the limbic area. In the animals rendered dependent on morphine, the results obtained were similar to those of butorphanol-dependent rats except for changes of 5-HIAA levels in some brain regions. These results suggest that an alteration of dopaminergic neuron activity following a reduction of DA and its metabolites in specific brain regions (e.g., striatum, limbic, midbrain, and pons/medulla) play an important role in the expression of the opioid withdrawal syndrome.

Animals↗

PubMed1996

Effects of repeated administration of a kappa-opioid agonist on phorbol ester binding to membrane-bound protein kinase C in rat brain.

The dissociation constant (KD) of [3H]phorbol 12,13-dibutyrate (PDBu) binding to protein kinase C (PKC) in membranes of rat cortex and midbrain was significantly decreased with no change in the receptor density (Bmax) following 7-d treatment with a kappa-opioid agonist, U-50,488 (20 mg/kg/d, i.p.). Neither the Bmax nor KD values in pons/medulla were altered by repeated U-50,488 treatment. These results suggest that repeated administration of a kappa-opioid agonist increases the affinity for PDBu binding to the membrane-bound PKC in rat cortex and midbrain, but not in pons/medulla.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1995

Comparative rewarding properties of morphine and butorphanol.

Because butorphanol (Stadol), a synthetic morphinan compound, has been demonstrated in our laboratories to produce physical dependence and withdrawal symptoms in rats, we have hypothesized that butorphanol has rewarding properties indicative of abuse potential. To test this hypothesis, the effects of equimolar doses of butorphanol tartrate (0.5-5.0 micrograms) and morphine sulfate (0.8-8.0 micrograms) were assessed in inbred Lewis male rats using the conditioned place preference (CPP) paradigm. Unilateral microinjections (1 microl/inj) of saline or opioids were made into the ventral tegmental area (VTA). Microinjections of saline to controls were associated with both sides of modified Skinner boxes, whereas opioid injections were associated only with the white chambers (less preferred side to the naive animals). Opioids were administered alternating with saline in the drug-treated animals on alternating days. During eight conditioning sessions the rats learned to associate light and dark sides of the Skinner boxes with microinjections of opioids or saline, respectively. Although all doses of morphine induced significant preference over saline, only the higher doses of butorphanol (2.0-5.0 micrograms) produced significant conditioned place preference for the sides of the chambers associated with the drugs. These results suggest that, like morphine which is widely abused, butorphanol also has rewarding properties, and, therefore, further investigations regarding its abuse potential are necessary.

Animals↗

PubMed1995

Influence of chronic opioid treatment on low Km GTPase activity in rat brain: evidence for the involvement of G-proteins in opioid tolerance.

To investigate G protein function during the initial state of opioid tolerance, low Km GTPase activity was measured following chronic treatment with morphine (mu agonist) and butorphanol (mu/delta/kappa mixed agonist) in rats. Chronic opioid administration (20 mg/kg, IP) was performed once a day for 7 consecutive days. Under these conditions, antinociceptive tolerance to morphine but not butorphanol was developed. Chronic morphine treatment enhanced basal low Km GTPase activity in the pons/medulla, but not in the cortex and midbrain. On the other hand, chronic butorphanol treatment had no effect on basal low Km GTPase activity. These results suggest that chronic in vivo treatment of rats with mu agonists leads to an increase in the hydrolysis of GTP to GDP, by a basal low Km GTPase activity of G-proteins in the pons/medulla and that an enhancement of GTPase activity in this specific area may contribute to the development of antinociceptive tolerance to mu agonists.

Animals↗

PubMed1995

The development of a consumer guide on the quality of obstetrical services: the Missouri experience.

Missouri published a consumer guide on obstetric in the spring of 1994. This article describes the events and processes that led to the publication of the guide. The guide provided obstetrical quality-of-care indicators on structure, process, and outcomes for each facility doing deliveries. The article describes the principles followed in developing the guide, how the indicators were chosen, how the guide was constructed, and what data sources were used. Several lessons were learned including: a guide opens communication within the provider community, development of a guide is a long process, an advisory committee and preliminary review of findings by providers are necessary, and strong technical expertise is essential.

Algorithms↗

PubMed1994

A protein kinase inhibitor, H-7, inhibits the development of tolerance to opioid antinociception.

To investigate the effect of a protein kinase inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), on the development of tolerance to antinociception induced by morphine (mu-opioid receptor agonist) and butorphanol (mu/delta/kappa-mixed opioid receptor agonist), rats were infused i.c.v. with morphine, butorphanol and H-7 through osmotic minipumps for 3 days. Concomitant infusion of H-7 dose dependently inhibited the development of tolerance to i.c.v. morphine- and butorphanol-induced antinociception. These results suggest that protein kinases may play an important role in the development of opioid tolerance.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1994

Repeated administration of opioids alters characteristics of membrane-bound phorbol ester binding in rat brain.

Scatchard analysis of saturation binding data indicated that dissociation constant (KD) of [3H]phorbol 12,13-dibutyrate (PDB) binding to the membrane-bound protein kinase C of rat cortex and midbrain was significantly decreased following systemic repeated administration of morphine (mu-opioid receptor agonist) and butorphanol (mu/delta/kappa-mixed opioid receptor agonist). No change in the receptor density (Bmax) of [3H]PDB binding was found following repeated treatment with morphine and butorphanol. On the other hand, neither the Bmax nor KD values in pons/medulla were altered in these rats. These results suggest that systemic repeated opioid treatment, such as morphine and butorphanol leads to an increased affinity for phorbol ester binding to the membrane-bound protein kinase C in rat cortex and midbrain.

Animals↗

PubMed1994

Enhancement of the rate of GTP hydrolysis in rat brain by repeated kappa-opioid treatment.

To investigate the G protein and protein kinase C (PKC) systems during the initial state of kappa-opioid tolerance, the low Km GTPase and PKC activities were measured following repeated treatment of rat with the kappa-agonist, U-50,488. In behavioral studies, antinociceptive tolerance to U-50,488 was developed following 7-day treatment with U-50,488. Under these conditions, repeated administration of U-50,488 significantly enhanced the basal low Km GTPase activity in the pons/medulla but not in the cortex and midbrain regions. On the other hand, repeated U-50,488 treatment had no effect on PKC activity in cytosol and membrane fractions under the calcium-chelating conditions. These results indicate that repeated administration of kappa-agonist, U-50,488, increases in the basal hydrolysis of GTP to GDP in rat pons/medulla but not PKC activity which was observed in the case of repeated administration with morphine in rats.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1994

Influence of chronic morphine treatment on protein kinase C activity: comparison with butorphanol and implication for opioid tolerance.

The aim of this study was to determine whether chronic opioid treatment could influence the protein kinase C (PKC) activity in the rat brain. Chronic morphine (microns agonist) but not butorphanol (mu/delta/kappa mixed agonist) treatment enhanced cytosolic PKC activity in the pons/medulla, but not in the cytosolic fractions of cortex and midbrain regions. Concomitant administration of the opioid receptor antagonist, naloxone, blocked the PKC upregulation by chronic morphine. Chronic administration of morphine and butorphanol produced no change in the membrane PKC activity. Antinociceptive tolerance to morphine but not to butorphanol was developed under these conditions. These results suggest that chronic morphine administration leads to an upregulation of the cytosolic PKC activity in the pons/medulla through repeated activation of mu opioid receptors and that the PKC upregulation in this specific area may contribute to the morphine tolerance.

Animals↗

PubMed1994

Involvement of kappa-opioid receptors in opioid dependence/withdrawal: studies using butorphanol.

The dependence liability of a class of opioid agonist/antagonist analgesics, e.g. pentazocine, butorphanol, and buprenorphine, is widely recognized. However, the relative involvement of mu-, delta-, and kappa-opioid receptors mediating physical dependence on these compounds is not completely known. In the present study, butorphanol dependence was produced by continuous intracerebroventricular (i.c.v.) infusion of butorphanol (26 nmol/h) for 3 days in male Sprague-Dawley rats. Nor-binaltorphimine, a long-acting kappa-opioid receptor antagonist, and naloxone, a nonspecific antagonist, were administered i.c.v. to precipitate withdrawal in butorphanol-dependent animals, so as to investigate the involvement of central kappa-opioid receptors in opioid dependence. ED50 ratios (naloxone/nor-binaltorphimine) for eliciting withdrawal signs were: teeth-chattering (1.25), yawning (2.13), and ejaculation (0.72). Our data indicate that nor-binaltorphimine precipitated withdrawal behaviors similar to those precipitated by naloxone. It appears that central kappa-opioid receptors may play a major role in the development of butorphanol dependence in rats.

Animals↗

PubMed1994

Cardiovascular toxicities of nandrolone and cocaine in spontaneously hypertensive rats.

The outcome of concurrent abuse of cocaine and anabolic steroids is largely unknown and merits investigation. The present study was designed to determine whether an animal model could be developed for investigation of the toxic responses to simultaneous administration of cocaine and an anabolic steroid, nandrolone decanoate. Twenty-four male spontaneously hypertensive rats (SHR), all 7 weeks of age, were assigned randomly to four groups: (1) control, (2) cocaine, (3) nandrolone, and (4) cocaine plus nandrolone. Metabolic measurements and indirect (tail-cuff) blood pressure and heart rate measurements were performed on all rats every 2 weeks. All drug treatment groups exhibited significantly (p < 0.05) higher levels of blood pressure after 6 weeks of treatment when compared to the control group. Cocaine plus nandrolone group exhibited the lowest heart rate compared to other groups. Rats were euthanized at 13 weeks of age, and different tissues were removed, blotted dry, and weighed. The kidney, levator ani muscle, and seminal vesicle (with prostate glands) weights in both nandrolone-receiving groups were higher than those of the control and cocaine groups. Testicular weights of the cocaine plus nandrolone group were less than those of the control and cocaine groups. Hearts were fixed in 10% buffered formaldehyde before myocardial dimension measurements were performed. The nandrolone group showed increased vertical ventricular diameters when compared to the control and cocaine groups. The nandrolone group also displayed higher vertical ventricular circumferences when compared to all the other groups. Finally, the cocaine plus nandrolone group had the greatest ventricular weights (per 100 g body weight) and left ventricular volumes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Tolerance development to butorphanol: comparison with morphine.

In order to evaluate and to compare the time course, dose response, and the degree of tolerance development to butorphanol and morphine, rats were continuously intracerebroventricularly (ICV) infused with saline vehicle (1 microliter/h), butorphanol (6.5, 13, 26, and 52 nmol/microliters/h), or morphine (1.6, 6.5, and 26 nmol/microliters/h) through osmotic minipumps for 1 to 3 days. The tail-flick responses were determined pre-, during, and postinfusion. Tolerance to morphine developed faster than that to butorphanol. The antinociceptive response to the ICV challenge dose (6 h after the termination of drug infusion) of butorphanol or morphine was decreased significantly and there was a negative correlation between the dose of the drug infused and the observed antinociceptive response. In terms of butorphanol and morphine tolerance, a parallel rightward shift in the dose-response curve was produced with the degree of shift proportional to the log of the infusion dose. In tail-flick tests, the shifts of the dose-response curves for butorphanol and morphine in tolerant animals were 11.8- and 46.3-fold, respectively. However, in the acetic acid writhing test, the shifts of the dose-response curves for butorphanol and morphine in tolerant animals were 11.3- and 11.7-fold, respectively. These results suggest that there is a greater degree of tolerance to morphine than there is to butorphanol, but the degree of butorphanol tolerance is still substantial. In addition, two pain assays (tail flick vs. writhing) yielded different estimations of tolerance in a comparison of morphine and butorphanol.

Animals↗

PubMed1994

Crosstolerance between butorphanol and morphine in rats.

To investigate the antinociceptive effects of morphine and U-50,488 after continuous administration with butorphanol, rats were intracerebroventricularly (ICV) infused with butorphanol (26 nmol/microliters/h) through osmotic minipumps for 3 days. Six hours after termination of infusion, the rats were challenged with different doses of morphine or U-50,488. Antinociceptive effects, as assessed by tail-flick and acetic acid writing tests, were measured 15 min after challenge. Development of crosstolerance to morphine was evident in butorphanol-infused animals. The study also revealed that crosstolerance to butorphanol developed in continuously ICV morphine-infused animals. Continuous ICV infusion with butorphanol produced a marked rightward shift of the antinociceptive dose-response curve resulting from U-50,488 challenge. These results showed that there is an antinociceptive crosstolerance between butorphanol and morphine, and crosstolerance to U-50,488 developed in continuously butorphanol-infused animals. The present data suggested that chronic ICV treatment with high doses of butorphanol can lead to desensitization of the antinociceptive systems mediated through the central kappa as well as mu receptors in rats.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1993

Involvement of delta-opioid receptors in physical dependence on butorphanol.

Butorphanol, a synthetic agonist/antagonist, has been shown to act on mu-, delta- and kappa-opioid receptors. However, the relative involvement of opioid receptor subtypes in mediating butorphanol dependence is not known. In the present study, naltrindole, a delta-selective non-peptide antagonist, was administered intracerebroventricularly (i.c.v.) to mask supraspinal delta-opioid receptors before and during the induction of butorphanol dependence. Treatment with naltrindole (0.1, 1, or 10 nmol/5 microliters per rat) significantly blocked naloxone-, a nonspecific antagonist, precipitated butorphanol withdrawal behaviors (escape behavior, teeth-chattering, wet shakes, forepaw tremors, ptosis, diarrhea, body weight loss, and hypothermia) at all doses tested, and decreased ejaculation at 0.1 nmol in butorphanol-infused rats. In contrast, naltrindole treatment had no effect on yawning, nor urination. These results indicate that central delta-opioid receptors are involved in mediating butorphanol dependence in rats.

Animals↗

PubMed1993

Effects of nor-binaltorphimine on butorphanol dependence.

Butorphanol has been shown to act on mu-, delta-, and kappa-opioid receptors. However, the relative involvement of different opioid receptor subtypes in butorphanol dependence is not known. In the present study, nor-binaltorphimine, a long-acting non-peptide kappa-opioid receptor antagonist, was employed to mask central kappa-opioid receptors before and during the induction of butorphanol dependence in rats, so that the involvement of kappa-opioid receptors could be elucidated. The results revealed that treatment with nor-binaltorphimine markedly blocked naloxone-precipitated withdrawal signs of escape behavior, teeth-chattering, wet shakes, ptosis, body weight loss, and hypothermia at all doses tested, and attenuated the withdrawal symptoms of forepaw tremors (24 nmol: P < 0.001) and diarrhea (12 nmol: P < 0.05; 24 nmol: P < 0.01). In contrast, nor-binaltorphimine had no effect on yawning, ejaculation, nor urination in butorphanol-infused rats undergoing withdrawal. Three days of butorphanol infusion significantly increased KD values (in the cortex and striatum), decreased Bmax (in the cortex only) of [3H]U-69,593 binding, and shifted Ki of nor-binaltorphimine against [3H]U-69,593 (4.5 nM) binding in the cortex by more than 10-fold. Treatment with nor-binaltorphimine blocked the effects of butorphanol on kappa-opioid receptors. It is therefore concluded that kappa-opioid receptors are involved in mediating escape behavior, teeth-chattering, wet shakes, forepaw tremors, ptosis, diarrhea, weight loss, and hypothermia in butorphanol-dependent rats undergoing withdrawal. Furthermore, kappa-opioid receptors become desensitized to agonists (in the cortex and striatum), down-regulated (in the cortex), and supersensitive to antagonists in butorphanol-dependent rats.

Animals↗

PubMed1993

Site and mechanism of behavioral tolerance to cocaine: a study of dopamine release in Wistar-Kyoto and spontaneously hypertensive rats.

Wistar-Kyoto and spontaneously hypertensive rats received i.v. infusions of cocaine hydrochloride (60 mg/kg per day) for 3, 7, and 14 days, or saline for 7 days. Acute cocaine challenge (40 mg/kg, s.c.) was given to treated and control rats 24 hr after the termination of each infusion period. There were no strain differences in brain levels of cocaine during cocaine infusion, nor after cocaine challenges. There were no strain differences in resting levels of [3H]dopamine release. Release of [3H]dopamine decreased in nuclei accumbens of 7- and 14-day cocaine-infused animals. Release of [3H]dopamine was maximal in both brain regions 2 hr after acute cocaine challenge. After 14 days of cocaine infusion, cocaine challenge in both strains reduced [3H]dopamine release in the nucleus accumbens, but not in the striatum; the reduction being greater in Wistar-Kyoto rats. The behavioral tolerance which accompanies similar cocaine infusion regimens may be related to striatal "tolerance" to cocaine-induced dopamine release.

Animals↗