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1.
Body Image ; 33: 199-206, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32305713

ABSTRACT

The body positive movement emerged in response to pressure to pursue the unattainable thin ideal, and promotes a more accepting stance towards the body. To date, however, little is known regarding the nature of online body positive content. Using publicly available data from a large online discussion platform (Reddit), all the forums to which commenters on a body acceptance forum (N = 1262) had also contributed were identified. For each pairing of 50 representative forums (i.e., a large number and proportion of body acceptance commenters), the commenter-overlap between the two forums was used to compute a network model, to detect communities of body acceptance commenters. By manually reviewing the topics of each community's forums, the shared interests of these commenters were identified. The majority of commenters (86 %) contributed to forums relating to women, feminism, relationships and support, and mental health. Large proportions of the commenters also revealed an interest in topics including body weight/shape, eating, exercise, and cosmetics. These findings confirm that original feminist tenets of body positivity remain present. However, our findings also suggest the existence of a sizeable subgroup interacting with topics related to the thin ideal, perhaps illustrating a gradual absorption of the body positive movement into mainstream culture.


Subject(s)
Body Image/psychology , Online Social Networking , Women/psychology , Adult , Female , Feminism , Humans
2.
Placenta ; 30(6): 536-8, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19345412

ABSTRACT

Having previously demonstrated that heme oxygenase (HO) is expressed on invasive trophoblast within the human placental bed, we have now further hypothesised that HO may play a role in trophoblast invasion. To begin to test this hypothesis we have used a well characterised in vitro model of trophoblast invasion to determine whether antibodies raised against HO-1 and HO-2, or selective inhibition of HO with the HO inhibitor zinc protoporhyrin-9 (Zn PP-9), would affect the invasive ability of trophoblast cells. Cytotrophoblast cells were purified from term human placenta then cultured on Matrigel-coated chambers in the presence or absence of HO antibodies or Zn PP-9. The HO-1 antibody had no effect on invasion whereas the presence of the HO-2 antibody significantly inhibition invasion (p<0.05). The presence of Zn PP-9 resulted in a significant reduction in invasion (p<0.05) whereas the vehicle alone had no effect. Taken together these results suggest, that at least in vitro, HO-2 may be important in controlling trophoblast invasion.


Subject(s)
Cell Movement/drug effects , Heme Oxygenase (Decyclizing)/antagonists & inhibitors , Protoporphyrins/pharmacology , Trophoblasts/drug effects , Antibodies/pharmacology , Cell Adhesion/drug effects , Cell Culture Techniques , Cells, Cultured , Enzyme Inhibitors/pharmacology , Female , Heme Oxygenase (Decyclizing)/immunology , Humans , Pregnancy , Trophoblasts/physiology
3.
Hypertens Pregnancy ; 28(3): 256-72, 2009.
Article in English | MEDLINE | ID: mdl-19263288

ABSTRACT

Heme oxygenases (HO-1 and HO-2) are responsible for the production of carbon monoxide, a vasodilator. The products of heme oxygenase are also anti-oxidants. HO is expressed within the placenta and is important in controlling placental blood flow. HO can be sensitive to oxygen, with responses differing depending on the cell type. Recent studies have suggested that in preeclampsia, the placenta would be subjected to fluctuations in oxygen tension analogous to an ischemia-reperfusion injury. Thus the present study tested the hypothesis that HO-1 and or HO-2 expression in placental villous explants would be altered by an ischemic-reperfusion insult. Human term placental explants were exposed to hypoxia then re-oxygenation in 5% or 20% O(2) or repeated cycles of hypoxia-re-oxygenation. HO protein concentrations were assessed by Western blotting. No changes in HO-1 or HO-2 were found with any treatment protocol. Chemical induction of HO-1 was possible in explants showing that HO-1 induction in explants is possible. The results suggest that cells in term placental villous tissue do not respond to hypoxia-re-oxygenation by altering the amount of HO-1 or HO-2 protein.


Subject(s)
Heme Oxygenase (Decyclizing)/metabolism , Heme Oxygenase-1/metabolism , Placenta/enzymology , Reperfusion Injury/metabolism , Blotting, Western , Female , Humans , Hypoxia/metabolism , Hypoxia/pathology , Immunohistochemistry , Oxygen/administration & dosage , Oxygen/metabolism , Placenta/pathology , Pregnancy , Reperfusion Injury/pathology
4.
Pharmacoepidemiol Drug Saf ; 17(11): 1123-30, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18816462

ABSTRACT

BACKGROUND: Information on prescribing practices in Palestine is lacking, however, still essential for strategic planning. PURPOSE: To characterise prescribing patterns and specific medicine use indicators in selected non-governmental organisations' (NGO) primary healthcare clinics/centres (PHC) in the West Bank (WB) in Palestine. METHODOLOGY: A prospective cross-sectional survey of prescribing practices based on medical records of 6032 patients with acute symptoms frequenting 41 NGO PHCs in the WB, between July and September 2004. A systematic random sample of every 10th patient appearing on the patient registration list was selected. Direct observation of consultation and dispensing practices and times in a sub-group of patients was completed utilising special forms. RESULTS: Respiratory tract infections were the most commonly occurring conditions. On average, 1.9 drugs were prescribed per encounter and antibiotics were the most commonly prescribed medications, followed by Analgesics and NSAIDs accounting for 46 and 20% of the total medications expenditures, respectively. Injections and combined medications use per encounter was 16 and 8%, respectively. Most commonly prescribed medications were of local production. Consultation (6.4 +/- 4.6 minutes) and dispensing times (1.6 +/- 1.5 minutes) were short with inadequate labelling. Provision of reference sources and treatment guidelines implementation were also inadequate. CONCLUSION: The results suggest that prescribing practices could be improved through wider implementation of treatment guidelines, a review of antibiotic prescribing, and increased time spent with patients to promote concordance. Strategies aimed at improving prescribing and dispensing practices should be addressed through new innovative capacity building models based on problem solving and feedback mechanisms.


Subject(s)
Ambulatory Care Facilities , Arabs , Drug Utilization Review , Practice Patterns, Physicians' , Prescription Drugs/therapeutic use , Primary Health Care , Private Sector , Adolescent , Adult , Ambulatory Care Facilities/economics , Ambulatory Care Facilities/statistics & numerical data , Arabs/statistics & numerical data , Cross-Sectional Studies , Drug Costs , Drug Labeling , Female , Guideline Adherence , Humans , Male , Middle East , Practice Guidelines as Topic , Practice Patterns, Physicians'/statistics & numerical data , Prescription Drugs/economics , Primary Health Care/economics , Primary Health Care/statistics & numerical data , Private Sector/economics , Private Sector/statistics & numerical data , Prospective Studies , Quality of Health Care , Referral and Consultation , Young Adult
5.
J Clin Pharm Ther ; 32(6): 545-56, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18021331

ABSTRACT

OBJECTIVE: To review the research literature to date on pharmacist prescribing in the United Kingdom (UK) and to explore the main areas of care and practice settings including any benefits and limitations. FINDINGS: There are two models of pharmacist prescribing in the UK: pharma\cist supplementary prescribing (SP) introduced in 2003, involving a voluntary partnership between the responsible independent prescriber (a physician or a dentist), the supplementary prescriber and the patient, to implement an agreed patient-specific clinical management plan; and pharmacist independent prescribing (IP) introduced in 2006, responsible for the assessment and consequent management, including prescribing of both undiagnosed and diagnosed conditions. There have been narrative reports of pharmacist SP in different health care settings including primary care, community pharmacies, secondary care and at the primary/secondary care interface; published research within these areas of care is conflicting as to which setting is more suitable for pharmacist prescribing. Initial research reports that almost 50% of pharmacist supplementary prescribers self-reported prescribing with both benefits of and barriers to implementing SP. Research involving other healthcare professionals has indicated that encroachment of traditional roles is likely to occur because of the advent of pharmacist prescribing. A small-scale study has concluded that patients are likely to accept pharmacist prescribing favourably, with another study showing pharmacist prescribing leading to improved adherence to guidelines. There is no published research yet available about practices involving pharmacist IP. DISCUSSION: Most of the literature focuses on pharmacists' perceptions of SP, with little information referring to other stakeholders, including patients. There is also limited published research focusing on clinical and economic outcomes of pharmacist SP. CONCLUSION: This is a rapidly changing aspect of pharmacy practice in the UK, particularly with the more recent introduction of pharmacist IP. It is likely that this area of research will expand rapidly over the coming years.


Subject(s)
Drug Prescriptions , Pharmacists , Humans , Professional Role , United Kingdom
6.
Neuropathol Appl Neurobiol ; 30(6): 683-91, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15541008

ABSTRACT

GADD34 is a growth arrest and DNA damage inducible gene up-regulated in response to DNA damage, cell cycle arrest and apoptosis. It is thought that GADD34 may play a crucial role in cell survival in ischaemia. GADD34 expression was assessed immunohistochemically in post-mortem human hippocampal tissue obtained from patients surviving for defined periods (0-24 h; 24 h-7 days) after a cardiac arrest and in age-matched control subjects. In control brain, cytoplasm staining in GADD34 immunopositive cells was faint but present throughout the hippocampus and cortex. There was minimal change in GADD34 expression in the group surviving 0-24 h after cardiac arrest. However GADD34 immunostaining was markedly increased in selectively vulnerable regions in the 24 h-7 day survival group. Increased GADD34 staining was present in ischaemic neurones and in some morphologically normal neurones after cardiac arrest. Extensive ischaemic damage was found to correlate with elevated GADD34 immunostaining in the CA1 layer of the hippocampus (**P < 0.0016). In addition, GADD34 was found to colocalize with proliferating cell nuclear antigen in some neurones. The up-regulation of GADD34 in response to global ischaemia in the human brain plus its influence on protein synthesis and DNA repair suggests that this protein may have the potential to influence cell survival.


Subject(s)
Antigens, Differentiation/biosynthesis , Brain Ischemia/metabolism , DNA Repair/genetics , Neoplasm Proteins/biosynthesis , Nerve Tissue Proteins/biosynthesis , Adolescent , Adult , Aged , Apoptosis , Brain Chemistry/physiology , Cell Cycle Proteins , Female , Heart Arrest/metabolism , Heart Arrest/pathology , Humans , Immunohistochemistry , Male , Middle Aged , Proliferating Cell Nuclear Antigen/biosynthesis , Proliferating Cell Nuclear Antigen/genetics , Protein Phosphatase 1 , Survival , Up-Regulation
7.
J Clin Pharm Ther ; 29(3): 273-7, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15153090

ABSTRACT

BACKGROUND: The role of long-term glycaemic control in minimizing long-term complications of diabetes mellitus is evidence-based and national guidelines recommend a target glycosylated haemoglobin level of approximately 7%. Although the role of self-monitoring blood and urine glucose is less well defined, this activity consumes vast National Health Service (NHS) resources. AIMS: The aims of this study were to (i) determine the current practice of glucose self-monitoring in primary care, (ii) determine any changes to therapy made as a result and (iii) compare monitoring and frequency of monitoring in those patients using insulin with those patients taking oral hypoglycaemic agents. METHODS: Postal questionnaire to 311 patients using insulin or oral hypoglycaemic agents identified from three general practices. RESULTS: The response rate was 59.8% (186/311), with the majority of responding patients (n = 158, 87.3%) performing self-monitoring. The patients using insulin were more likely to be self-monitoring than those taking oral therapy (chi(2), P < 0.001, d.f. = 1). The majority of patients who self-monitored and were using insulin (n = 45, 61.1%) altered the dose of insulin if a reading was beyond their target range. However, the majority of patients who self-monitored and were taking oral therapy (n = 48, 68.6%) took no action at all. CONCLUSIONS: Blood glucose self-monitoring was common in those treated with insulin or oral hypoglycaemics, although those using insulin were more likely to self-monitor. Notably many patients, particularly those on oral therapy, took no action based on the results of self-monitoring.


Subject(s)
Blood Glucose Self-Monitoring/methods , Evidence-Based Medicine , Primary Health Care , Administration, Oral , Aged , Attitude to Health , Blood Glucose Self-Monitoring/statistics & numerical data , Data Collection , Evidence-Based Medicine/methods , Glycosuria , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/classification , Hypoglycemic Agents/therapeutic use , Insulin/administration & dosage , Insulin/therapeutic use , Middle Aged , Surveys and Questionnaires
8.
Pharm World Sci ; 23(5): 173-4, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11721670

ABSTRACT

OBJECTIVE: To determine patient's opinions regarding the changeover from CFC containing to CFC-free salbutamol. DESIGN: Patients receiving metered dose salbutamol inhaler therapy were identified and verbal consent was obtained before a semi-structured interview was performed. Setting An outpatient respiratory clinic within a busy teaching hospita. MAIN OUTCOME MEASURES: Knowledge of CFC-free inhaler therapy and acceptance of change. RESULTS: A total of 28 patients were identified of whom only eight (29%) had been changed to a CFC-free product. Six of these (75%) had received counselling from their GP or pharmacist regarding the change. Differences were reported by all of the patients who had been changed to a CFC-free inhaler with comments including difference in taste (6 patients), difference in feel (6), less effective (1) and more effective (1). Three patients preferred the CFC-free inhaler to their previous therapy. Although 13 out of the 20 patients who had not received a CFC-free inhaler stated they were happy with the potential changeover, 10 (80%) has concerns relating to effectiveness. CONCLUSION: The majority of patients still receiving CFC inhalers were aware that the production of CFC-containing products had been restricted although they were unaware of the imminent changes that would take place regarding their inhaler therapy. However, the small sample size recruited in this study may mean that the results are unrepresentative of the CFC-free implementation process in the Grampian Health Board area as a whole. Nonetheless, in view of the differences experienced by patients who received CFC-free inhalers and the concerns stated about potential lack of efficacy by patients about to be changed over, it is essential that healthcare professionals provide advice on CFC-free inhalers to all patients.


Subject(s)
Air Pollutants , Chlorofluorocarbons , Nebulizers and Vaporizers/statistics & numerical data , Patient Satisfaction/statistics & numerical data , Primary Health Care/statistics & numerical data , Air Pollutants/adverse effects , Albuterol/therapeutic use , Bronchodilator Agents/therapeutic use , Chlorofluorocarbons/adverse effects , Female , Humans , Male , Nebulizers and Vaporizers/trends , Outpatients/statistics & numerical data
9.
Health Bull (Edinb) ; 53(6): 359-64, 1995 Nov.
Article in English | MEDLINE | ID: mdl-8530294

ABSTRACT

The aim of the study was to compare the antibiotic treatment actually received by elderly, hospitalised patients with urinary tract infection (UTI) with 'optimal' therapy (as gauged by compliance with antibiotic policy, infecting organism, sensitivity data, patient renal function and cost). UTI was more common in females and in catheterised patients and E.Coli was the commonest pathogen. Trimethoprim and co-amoxiclav were the drugs used most frequently for either empirical or sensitivity data-based treatment. In 96% of infections a drug with appropriate action was administered. Often, however, treatment could have been optimised by substituting a cheaper suitable antibiotic, by standardising duration of therapy and ensuring that doses were adjusted for renal impairment. Savings from the use of 'optimal' therapy were estimated at 17%. There is clearly considerable scope for positive input from the clinical pharmacist in this area.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Medical Audit , Urinary Tract Infections/drug therapy , Aged , Aged, 80 and over , Clinical Protocols , Costs and Cost Analysis , Female , Humans , Male , Scotland , Urinary Tract Infections/economics , Urinary Tract Infections/etiology
10.
Eur J Pharmacol ; 249(1): 53-63, 1993 Nov 02.
Article in English | MEDLINE | ID: mdl-8282019

ABSTRACT

The voltage-dependent Ca2+ channel blocker, verapamil, and the calmodulin antagonist, trifluoperazine, each reduced resting tone and attenuated constriction induced by acetylcholine or vagal stimulation in normal guinea-pig trachea. Attenuation of vagal responses involved both pre- and post-junctional effects on cholinergic neurotransmission. In albumin-sensitized trachea both drugs caused small increases in resting tone. Vagally mediated constrictor responses were resistant to attenuation by verapamil in sensitized trachea. Trifluoperazine was less effective against acetylcholine-induced tone in sensitized, as compared to untreated, trachea. The results indicate that Ca2+ handling is altered in airway smooth muscle in this animal model of bronchial asthma. Abnormal Ca2+ handling, therefore, may underlie the hyperresponsiveness to vagal input exhibited in sensitized trachea and could contribute to the generalised airway hyperreactivity characteristic of asthma.


Subject(s)
Asthma/physiopathology , Trachea/drug effects , Trifluoperazine/pharmacology , Verapamil/pharmacology , Acetylcholine/pharmacology , Albumins , Animals , Calcium/metabolism , Disease Models, Animal , Guinea Pigs , Immunization , Male , Muscle, Smooth/drug effects , Muscle, Smooth/physiopathology , Trachea/physiopathology , Vagus Nerve/drug effects , Vagus Nerve/physiology
11.
J Pharm Pharmacol ; 44(10): 817-23, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1360507

ABSTRACT

The effects of the K(+)-channel activator, cromakalim, on spontaneous tone and constrictor responses to vagal stimulation or acetylcholine were compared in trachea isolated from groups of guinea-pigs that were: untreated; sensitized and chronically exposed to inhaled albumin; or sham sensitized. Responses were assessed as changes in intraluminal pressure in the isolated, Krebs-filled trachea, increases and decreases in intraluminal pressure directly reflecting constriction and dilatation, respectively. Cromakalim reduced resting intraluminal pressure in normal trachea but in sensitized trachea mixed effects occurred, many preparations exhibiting increases in intraluminal pressure, particularly at lower concentrations of cromakalim. Cromakalim attenuated the frequency-dependent increases in intraluminal pressure evoked by stimulation of the vagus nerve in a concentration-dependent manner and to a similar degree in trachea from each of the three groups tested. The degree of attenuation was similar in the absence and presence of the cyclo-oxygenase inhibitor flurbiprofen. In untreated trachea, responses to a range of concentrations of applied acetylcholine were attenuated by cromakalim. In sensitized trachea the response to the lowest concentration of applied acetylcholine was attenuated by cromakalim but responses to higher concentrations of were unaffected. The results indicate that the direct relaxant effect of cromakalim is altered in sensitized trachea, which may indicate abnormal K(+)-channel behaviour in the smooth muscle cell membrane. Attenuation by cromakalim of vagal responses occurs in both normal and sensitized trachea, due chiefly to a pre-junctional effect on cholinergic neurotransmission which is independent of the generation of cyclo-oxygenase products.


Subject(s)
Albumins/immunology , Asthma/physiopathology , Benzopyrans/pharmacology , Bronchodilator Agents/pharmacology , Pyrroles/pharmacology , Trachea/drug effects , Acetylcholine/pharmacology , Animals , Cromakalim , Disease Models, Animal , Electric Stimulation , Flurbiprofen/pharmacology , Guinea Pigs , Immunization , In Vitro Techniques , Male , Potassium Channels/drug effects
12.
Br J Pharmacol ; 104(2): 343-8, 1991 Oct.
Article in English | MEDLINE | ID: mdl-1724625

ABSTRACT

1. The effects of calcium modulators on tracheal constriction evoked by vagal stimulation were examined in the isolated, innervated trachea of the guinea-pig. Responses were assessed in the Krebs-filled trachea as changes in intraluminal pressure (ILP), increases and decreases reflecting constriction and dilatation, respectively. 2. Preparations had a positive resting ILP, indicating significant spontaneous tone. Verapamil and nifedipine reduced baseline ILP, whilst Bay K 8644 had mixed effects. 3. Verapamil and nifedipine attenuated vagal responses in a concentration-dependent manner. At lower concentrations attenuation was due entirely to postjunctional effects but at higher concentrations prejunctional effects may have contributed to attenuation. 4. Verapamil and nifedipine attenuated vagal responses in the absence or presence of flurbiprofen, indicating that their effects are largely independent of the generation of cyclo-oxygenase products. Nifedipine, however, was less effective in reducing responses to low frequency vagal stimulation (up to 5 Hz) when flurbiprofen was present. 5. Bay K 8644 augmented vagal responses, the degree varying widely between preparations. 6. It was concluded that influx of Ca2+ through voltage-operated Ca2+ channels contributes significantly to vagally-mediated tracheal constriction in normal trachea and in trachea where endogenous release of cyclo-oxygenase products is inhibited.


Subject(s)
Bronchoconstrictor Agents/pharmacology , Trachea/drug effects , Vagus Nerve/drug effects , 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/pharmacology , Animals , Cyclooxygenase Inhibitors/pharmacology , Electric Stimulation , Flurbiprofen/pharmacology , Guinea Pigs , In Vitro Techniques , Male , Nifedipine/pharmacology , Trachea/innervation , Verapamil/pharmacology
13.
Br J Pharmacol ; 98(2): 662-8, 1989 Oct.
Article in English | MEDLINE | ID: mdl-2819338

ABSTRACT

1. Cromakalim reduced intraluminal pressure in the guinea-pig isolated, innervated trachea. 2. Preganglionic stimulation of the cervical vagus nerve elicited a frequency-dependent increase in intraluminal pressure. Cromakalim attenuated responses to vagal stimulation in a concentration-dependent manner at all frequencies tested. 3. Field stimulation caused a frequency-dependent increase in intraluminal pressure mediated by muscarinic cholinoceptors. Cromakalim did not affect the amplitude of responses at any frequency of stimulation, even at high concentrations. 4. Acetylcholine, added to the Krebs solution bathing the adventitial surface of the trachea, evoked a concentration-dependent increase in intraluminal pressure. The concentration-effect curve for acetylcholine was unaltered in the presence of cromakalim. 5. It is concluded that cromakalim modulates cholinergic neuroeffector transmission in the trachea chiefly by a prejunctional mechanism. However, cromakalim probably does not interfere with acetylcholine release from postganglionic cholinergic neurones.


Subject(s)
Benzopyrans/pharmacology , Bronchi/drug effects , Parasympathetic Nervous System/physiology , Parasympatholytics/pharmacology , Pyrroles/pharmacology , Acetylcholine/pharmacology , Animals , Cromakalim , Electric Stimulation , Guinea Pigs , In Vitro Techniques , Male , Muscle Relaxation/drug effects , Muscle, Smooth/drug effects , Trachea/innervation , Trachea/physiology , Vagus Nerve/physiology
14.
Br J Pharmacol ; 94(3): 729-36, 1988 Jul.
Article in English | MEDLINE | ID: mdl-3052679

ABSTRACT

1. The effects of leukotriene D4 (LTD4) on mechanical and electrical activity were examined in guinea-pig isolated trachealis muscle and compared with two other bronchoconstrictors, methacholine and potassium chloride (KCl). 2. LTD4 elicited concentration-dependent increases in tension in trachealis muscle which were slower in time course than responses induced by either methacholine or KCl. The maximum response to LTD4 was approximately 85% of the methacholine maximum. 3. At a concentration close to the EC50 for tension changes, LTD4 had no significant effect on either transmembrane potential or slow wave activity recorded in single trachealis cells. 4. At a concentration close to the EC90 for tension changes, LTD4 caused significant membrane depolarization, transiently reduced the amplitude and increased the frequency of slow wave discharge and ultimately abolished slow wave discharge. LTD4-induced depolarization was less marked, and developed more slowly, than that evoked by either methacholine or KCl. 5. These results show that LTD4 can elicit substantial increases in tension without altering transmembrane potential and are consistent with the view that LTD4 initiates contraction mainly through potential-independent mechanisms. However, at high concentrations the depolarization evoked by LTD4 allows the possibility that potential-dependent mechanisms may contribute to the spasm.


Subject(s)
Airway Resistance/drug effects , SRS-A/pharmacology , Animals , Flurbiprofen/pharmacology , Guinea Pigs , In Vitro Techniques , Male , Membrane Potentials/drug effects , Methacholine Chloride , Methacholine Compounds/pharmacology , Potassium Chloride/pharmacology , Trachea/drug effects
15.
Br J Pharmacol ; 92(4): 809-16, 1987 Dec.
Article in English | MEDLINE | ID: mdl-3427280

ABSTRACT

1 Mechanical and electrical responses to stimulation of the parasympathetic and sympathetic nerves were compared in the trachea isolated from normal guinea-pigs and from guinea-pigs sensitized to albumin and exposed repeatedly to inhaled albumin (a model of bronchial asthma). 2 Sensitized trachealis exhibited mechanical hyper-responsiveness to vagal stimulation characterized by a shift to the left of the frequency-response relationship and a 71% increase in the maximum response. 3 Transmembrane potential was significantly less negative in sensitized trachealis cells. 4 The amplitude of the depolarization evoked by vagal stimulation (4 or more pulses) was significantly greater in sensitized tissues. Vagally-mediated depolarization was associated with the appearance of regenerative electrical activity (spikes) in sensitized but not in control tissues. 5 Spontaneous discharge of slow waves occurred in cells from both control and sensitized trachea but the proportion of spontaneously active cells was higher in sensitized tissues. Spontaneous depolarization, like nerve-mediated depolarization, gave rise to abortive spikes only in sensitized trachealis. 6 Inhibitory responses to stimulation of the sympathetic stellate ganglion, mediated by beta-adrenoceptors, were unaltered in sensitized trachealis. 7 Possible explanations for the hyper-responsiveness to vagal input in sensitized trachealis are discussed.


Subject(s)
Albumins/pharmacology , Autonomic Nervous System/drug effects , Muscle, Smooth/drug effects , Animals , Electric Stimulation , Evoked Potentials/drug effects , Guinea Pigs , In Vitro Techniques , Male , Stellate Ganglion/physiology , Sympathetic Nervous System/physiology , Trachea/cytology , Trachea/drug effects , Vagus Nerve/physiology
16.
Br J Pharmacol ; 91(2): 385-94, 1987 Jun.
Article in English | MEDLINE | ID: mdl-3607363

ABSTRACT

Mechanical and electrical responses to stimulation of the vagus nerve were studied in the isolated, innervated trachea of the guinea-pig. In approximately half the preparations tested, the amplitudes of mechanical constrictor responses to stimulation of the vagus were reduced substantially during a period of sympathetic stimulation. Vagal responses were unaltered in the remainder. In single trachealis cells, stimulation of the vagus nerve or sympathetic stellate ganglion elicited depolarization and hyperpolarization, respectively. Vagally-mediated depolarization was decreased, unchanged or increased in amplitude after a period of sympathetic stimulation. Isoprenaline almost abolished mechanical responses induced by stimulation of the vagus, and this effect was blocked by propranolol. Noradrenaline attenuated markedly vagal mechanical responses also, and this effect was blocked by a combination of propranolol and phentolamine. Both noradrenaline and isoprenaline hyperpolarized single trachealis cells and greatly reduced the amplitude of vagally-mediated depolarization. Neither sympathetic stimulation nor applied catecholamines altered mechanical responses to applied acetylcholine, strongly suggesting that their effects on vagal responses are predominantly presynaptic.


Subject(s)
Isoproterenol/pharmacology , Norepinephrine/pharmacology , Stellate Ganglion/physiology , Trachea/innervation , Vagus Nerve/physiology , Acetylcholine/pharmacology , Animals , Electric Stimulation , Guinea Pigs , In Vitro Techniques , Male , Membrane Potentials/drug effects , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Trachea/drug effects , Trachea/physiology
17.
Br J Pharmacol ; 89(4): 793-801, 1986 Dec.
Article in English | MEDLINE | ID: mdl-3028552

ABSTRACT

Intracellular recordings were made from cells of the guinea-pig trachealis muscle. Some cells were electrically quiescent while others exhibited spontaneous slow waves. In quiescent cells, stimulation of the cervical vagus nerve evoked transient depolarization. Occasionally there was a single depolarization, but more often there were several fluctuations in potential. In spontaneously active cells, vagal stimulation induced a transient increase in amplitude of the slow waves without affecting their frequency. Depolarizing responses could be obtained with a single pulse applied to the vagus nerve, and responses increased in amplitude with number of pulses (up to 16 pulses), and with frequency of stimulation (up to 20 Hz). Depolarization did not give rise to spike discharge. Responses to vagal stimulation were blocked by atropine. In the presence of neostigmine, vagally-mediated depolarization was augmented and abortive spikes were observed in a number of cells. In quiescent cells, repetitive stimulation of the sympathetic stellate ganglion evoked slight hyperpolarization. In spontaneously active cells, sympathetic stimulation evoked attenuation, or temporary cessation of slow wave discharge, with or without hyperpolarization. Sympathetic-induced hyperpolarization and suppression of slow waves were both blocked by propranolol, but unaffected by phentolamine. Electrical changes associated with sympathetic stimulation may be of minor importance in the initiation of relaxation.


Subject(s)
Muscle, Smooth/physiology , Neuroeffector Junction/physiology , Animals , Atropine/pharmacology , Calcium/physiology , Electric Stimulation , Electrophysiology , Guinea Pigs , In Vitro Techniques , Male , Neostigmine/pharmacology , Propranolol/pharmacology , Sympathetic Nervous System/physiology , Synaptic Transmission/drug effects , Temperature , Trachea/innervation , Trachea/physiology , Vagus Nerve/physiology
18.
Br J Pharmacol ; 88(1): 239-48, 1986 May.
Article in English | MEDLINE | ID: mdl-2871883

ABSTRACT

Intraluminal pressure was measured in the isolated, fluid-filled trachea of the guinea pig, with autonomic innervation on the right side intact. Increases or decreases in intraluminal pressure reflected excitatory or inhibitory responses respectively, in the tracheal smooth muscle. Stimulation of the cervical vagus nerve evoked a cholinergic excitatory response. After cholinergic blockade with atropine, a non-adrenergic, non-cholinergic inhibitory response was obtained. Stimulation of the cervical sympathetic trunk, or stellate ganglion, evoked beta-adrenergic inhibitory responses. In the presence of propranolol, sympathetic stimulation evoked alpha-adrenergic excitatory responses which were of low amplitude (less than or equal to 5% of cholinergic excitatory responses). In the presence of phentolamine but not prazosin, beta-adrenergic inhibitory responses were potentiated. Neostigmine potentiated responses to vagal stimulation, increasing the amplitude and duration of response. At higher concentrations neostigmine (i) raised intraluminal pressure, a response blocked by atropine, and (ii) attenuated sympathetic inhibitory responses, an effect largely blocked by atropine. Histamine increased intraluminal pressure and this response was attenuated by atropine. In the presence of histamine, vagal excitatory responses were attenuated. Sympathetic inhibitory responses at low frequencies of stimulation (up to 10 Hz) were inhibited by histamine. 5-Hydroxytryptamine (5-HT) increased intraluminal pressure also, an effect partially blocked by atropine. 5-HT had no effect on vagal excitatory responses. Like histamine, 5-HT attenuated sympathetic inhibitory responses at lower frequencies of stimulation.


Subject(s)
Autonomic Agents/pharmacology , Autonomic Nervous System/drug effects , Histamine/pharmacology , Muscle, Smooth/drug effects , Serotonin/pharmacology , Adrenergic alpha-Agonists/pharmacology , Adrenergic beta-Antagonists/pharmacology , Animals , Electric Stimulation , Guinea Pigs , In Vitro Techniques , Male , Muscle, Smooth/physiology , Neostigmine/pharmacology , Parasympatholytics/pharmacology , Stellate Ganglion/drug effects , Stellate Ganglion/physiology , Sympatholytics/pharmacology , Trachea/drug effects , Trachea/innervation , Vagus Nerve/physiology
19.
J Membr Biol ; 81(1): 19-27, 1984.
Article in English | MEDLINE | ID: mdl-6492126

ABSTRACT

Tissue composition, membrane potentials and cellular activity of potassium, sodium and chloride have been measured in innervated and denervated rat skeletal muscles incubated in vitro. After denervation for 3 days, tissue water, sodium and chloride were increased but cellular potassium content and measured activity were little affected, despite a decrease of 16 mV in resting membrane potential which would have necessitated a decrease in cellular potassium activity of almost 50% were potassium distributed at electrochemical equilibrium. These findings, therefore, preclude a decreased electrochemical potential gradient for potassium as the cause of the membrane depolarization characteristic of denervated muscle fibers. Analysis of the data excludes an important contribution of rheogenic sodium transport to the resting potential of innervated muscles. These results strongly support the hypothesis that the decreased membrane potential in denervated fibers reflects a relative increase in the membrane permeability to sodium.


Subject(s)
Muscle Denervation , Muscles/metabolism , Animals , Chlorides/metabolism , Electrochemistry , In Vitro Techniques , Membrane Potentials , Potassium/metabolism , Rats , Rats, Inbred Strains , Sodium/metabolism
20.
J Membr Biol ; 81(1): 9-17, 1984.
Article in English | MEDLINE | ID: mdl-6492131

ABSTRACT

Measurement of intracellular chloride activity in the extensor digitorum longus (EDL) muscle of the rat using liquid ion-exchanger microelectrodes gave an apparent resting value of 10 to 11 mmol liter-1. If chloride ions were distributed passively across the muscle fiber membrane the predicted value would be 4 mmol liter-1. In experiments in which the bathing fluid was changed by (a) reduction of external chloride, or incubation at low external chloride followed by a return to normal concentrations, (b) an increase or reduction in external potassium, (c) alteration in potassium and chloride in the bathing medium so as to maintain a constant [K] X [Cl] product, or in other experiments in which the membrane potential was caused to change by anoxia, or by addition of ouabain to the medium, changes in intracellular chloride activity were invariably consistent with the hypothesis that this ion is passively distributed. Measurements of intracellular chloride activity with recessed-tip solid-state Ag/AgCl electrodes gave a value of 4.6 mmol liter-1. Since the liquid ion-exchanger is known to be poorly selective for chloride, it is concluded that the chloride ion is passively distributed in rat EDL muscle.


Subject(s)
Chlorides/metabolism , Muscles/metabolism , Animals , Cell Membrane Permeability , Chlorides/pharmacology , Hypoxia/metabolism , In Vitro Techniques , Membrane Potentials , Microelectrodes , Ouabain/pharmacology , Potassium/pharmacology , Rats , Rats, Inbred Strains
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