RESUMO
BACKGROUND: Statins are very effective in reducing coronary disease and ischaemic stroke but guidelines although evolving have not been clear on statin dose. AIM: To audit and review community statin prescribing. METHODS: A retrospective audit of the type and dose of statin dispensed was undertaken at five pharmacies in and around Perth, the capital city of Western Australia. Patients were de-identified. RESULTS: Statins made up 6.5% of all prescriptions. Statin dose when adjusted for different potency effectively varied 64-fold between patients. Rosuvastatin and atorvastatin accounted for 79% of prescriptions, at a mean dose of 10 times the effective dose 50. CONCLUSION: The extraordinarily wide variation in statin dose is at odds with the more consistent doses of other drugs used in the management of arterial disease. Unnecessarily high statin dosing increases side-effects and may not improve clinical outcomes appreciably. Rational prescribing of statins based on the pharmacodynamic evidence, with lower doses in most patients, combined with close attention to reduction of smoking, blood pressure and weight, is likely to reduce arterial disease most efficiently and safely.
Assuntos
Prescrições de Medicamentos/estatística & dados numéricos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Padrões de Prática Médica/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Doença das Coronárias/prevenção & controle , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/prevenção & controle , Austrália OcidentalRESUMO
BACKGROUND: This exploratory study examined parents' experiences with "Growing at Home" (G@H), a remote patient monitoring program for stable infants discharged from the Neonatal Intensive Care Unit (NICU) with continued need for nasogastric tube feeding. METHODS: We used classical content analysis to identify and refine emergent themes from 13 semi-structured key informant interviews. RESULTS: The primary emergent theme was the desire to return to normalcy, which was expressed as a primary motivator for participating in G@H. Parents reported G@H assisted them in transitioning from the NICU's highly medicalized setting to establishing a new normal with incorporation of their infant into their lives and families. Parental preparation is important, as some parents experienced challenges that indicate the program may not be suitable for all families. CONCLUSIONS: Parental experiences offer insight into benefits and challenges of early discharge from the NICU and highlight opportunities to support families beginning in the NICU and as they transition home.
Assuntos
Unidades de Terapia Intensiva Neonatal , Alta do Paciente , Recém-Nascido , Lactente , Humanos , Nutrição Enteral , Pais , Intubação GastrointestinalRESUMO
We report structurally tuned superconductivity in a K(x)Fe(2-y)Se(2-z)S(z) (0 ≤ z ≤ 2) phase diagram. Superconducting T(c) is suppressed as S is incorporated into the lattice, eventually vanishing at 80% of S. The magnetic and conductivity properties can be related to stoichiometry on a poorly occupied Fe1 site and the local environment of a nearly fully occupied Fe2 site. The decreasing T(c) coincides with the increasing Fe1 occupancy and the overall increase in Fe stoichiometry from z = 0 to z = 2. Our results indicate that the irregularity of the Fe2-Se/S tetrahedron is an important controlling parameter that can be used to tune the ground state in the new superconductor family.
RESUMO
Micro-fabricated bi-prisms have been used to create an interference pattern from an incident hard X-ray beam, and the intensity of the pattern probed with fluorescence from a 30 nm-thick metal film. Maximum fringe visibility exceeded 0.9 owing to the nano-sized probe and the choice of single-crystal prism material. A full near-field analysis is necessary to describe the fringe field intensities, and the transverse coherence lengths were extracted at APS beamline 8-ID-I. It is also shown that the maximum number of fringes is dependent only on the complex refractive index of the prism material.
RESUMO
The accidental or intentional ingestion of urine sugar reagent (Clinitest) tablets, a potent caustic, has been reported to cause severe esophageal mucosal damage and stricture formation. Gastric mucosal damage was reported once before in a man who intentionally ingested 26 Clinitest tablets. We encountered a case of accidental Clinitest tablet ingestion causing gastric and duodenal ulceration without esophageal damage, a previously undescribed complication of inadvertent Clinitest tablet ingestion. Our case reemphasizes the role of early fiberoptic endoscopy in the evaluation of caustic ingestions.
Assuntos
Citratos/intoxicação , Ácido Cítrico , Sulfato de Cobre , Úlcera Duodenal/induzido quimicamente , Indicadores e Reagentes/intoxicação , Bicarbonato de Sódio , Úlcera Gástrica/induzido quimicamente , Acidentes , Complicações do Diabetes , Combinação de Medicamentos/intoxicação , Úlcera Duodenal/diagnóstico , Duodenoscopia , Gastroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Gástrica/diagnósticoRESUMO
The activity of MK-467, a new peripherally acting alpha 2-antagonist, was assessed in volunteers by a randomized, double-blind, crossover design. One hour after administration of either 15 mg or 30 mg MK-467 or placebo, 200 micrograms clonidine was given intravenously and observations were made for a further 8 hours. Clonidine reduced plasma norepinephrine levels to 79% +/- 7% of that of control 1 hour after infusion, an effect that was antagonized by low-dose MK-467 (p less than 0.05). Mean systolic blood pressure increased by 4 mm Hg in the first hour after the 30 mg dose of MK-467 (p less than 0.01), although there was no significant difference between the 3 study days in the maximal clonidine-induced decrease in systolic pressure, diastolic pressure, or heart rate. Clonidine induced a peak increase in mean blood glucose of 13%, which was antagonized by both doses of MK-467 (p less than 0.05). Plasma insulin was suppressed by clonidine from 72 +/- 14 to 47 +/- 7 IU.L-1, an effect antagonised by both doses of MK-467 (p less than 0.05 in each case). MK-467 had no effect on clonidine-induced increased drowsiness, xerostomia, or increase in growth hormone secretion, which is consistent with it being a peripherally acting specific alpha 2-antagonist. The small effect of MK-467 on clonidine-induced changes in plasma glucose and insulin suggests that peripheral alpha 2-adrenergic receptors play only a minor role in normal glucose homeostasis.
Assuntos
Antagonistas Adrenérgicos alfa/farmacologia , Clonidina/antagonistas & inibidores , Quinolizinas/farmacologia , Administração Oral , Adulto , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Clonidina/farmacologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Humanos , Insulina/sangue , Masculino , Norepinefrina/sangue , Distribuição Aleatória , Salivação/efeitos dos fármacosRESUMO
To determine the systemic absorption of epinephrine when it is given by inhalation, six normal volunteers were given 15 puffs, followed by 30 puffs, of epinephrine from a pressurized aerosol (160 micrograms epinephrine/puff). The peak mean (+/- SE) plasma epinephrine levels were 1.50 (+/- 0.61) and 4.22 (+/- 1.93) nmol/L 1 minute after each dose, respectively. The effect on physiologic finger tremor correlated with the plasma epinephrine level and returned to baseline 20 minutes after taking the higher dose. There was a small fall in mean plasma potassium levels of 0.45 mmol/L and a small rise in plasma glucose levels of 0.81 mmol/L. On a separate occasion an injection of 0.3 ml of 1/1000 (300 micrograms) epinephrine was given subcutaneously to the same individuals. This caused a peak plasma epinephrine level of 2.43 (+/- 0.47) nmol/L at 10 minutes, and this was still raised at 2.05 (+/- 0.41) nmol/L after 40 minutes. The maximum fall in the mean plasma potassium level was 0.43 mmol/L after the injection.
Assuntos
Epinefrina/metabolismo , Absorção , Adulto , Aerossóis , Glicemia , Método Duplo-Cego , Epinefrina/administração & dosagem , Epinefrina/sangue , Frequência Cardíaca/efeitos dos fármacos , Humanos , Injeções Subcutâneas , Masculino , Potássio/sangue , Distribuição Aleatória , Tremor/induzido quimicamenteRESUMO
The specific airway conductance (sGaw) response of eight normal men to inhaled salbutamol, 200, 600, and 1800 micrograms, was measured on 3 separate days. On each occasion subjects received either placebo, long-acting propranolol (160 mg), or penbutolol (40 mg) orally in a double-blind manner after baseline lung function determination. After placebo, mean sGaw rose from a baseline of 2.07 +/- 0.15 to 2.81 +/- 0.25 kPa-1 X sec-1 after 200 micrograms salbutamol. There was little further airway dilation with higher doses of salbutamol. With long-acting propranolol, there was no significant airway dilation after 200 micrograms salbutamol but there was after 600 and 1800 micrograms inhaled salbutamol; baseline sGaw rose from 2.02 +/- 0.17 to 2.70 +/- 0.28 and 2.95 +/- 0.32 kPa-1 X sec-1. Penbutolol prevented any significant airway dilation with all doses of salbutamol. Penbutolol at the doses used appears to be a more potent blocker of beta 2-receptors than does propranolol.
Assuntos
Albuterol/farmacologia , Brônquios/efeitos dos fármacos , Pembutolol/farmacologia , Propanolaminas/farmacologia , Propranolol/farmacologia , Adulto , Pressão Sanguínea/efeitos dos fármacos , Dilatação , Método Duplo-Cego , Interações Medicamentosas , Frequência Cardíaca/efeitos dos fármacos , Humanos , MasculinoRESUMO
MK-912, a new alpha 2-adrenoceptor antagonist, was assessed in six volunteers by use of antagonism of the effects of intravenous clonidine as the main index of response. Subjects received single doses of either 0.2 or 2 mg of orally administered MK-912 or placebo in a randomized, double-blind, balanced, crossover design. Clonidine was infused intravenously over 10 minutes, 1 hour after dosing, and observations were made for 8 hours. The 2 mg dose of MK-912 significantly inhibited the clonidine-induced hypotension, bradycardia, xerostomia, and increase in plasma glucose concentrations that were observed during the placebo treatment period (p less than 0.05). The peak elevation in plasma growth hormone that was produced by clonidine on the day the placebo was given was inhibited an average of 87% by the 2 mg dose of MK-912 (p less than 0.01). Although there was a trend toward antagonism of clonidine by the 0.2 mg dose of MK-912, statistically significant differences from placebo were not consistently demonstrated for most parameters. However, a mean 59% inhibition of the clonidine-induced peak elevation of plasma growth hormone was observed (p less than 0.05). Oral MK-912 almost completely inhibits the effect of 200 micrograms of intravenous clonidine in human subjects, which is consistent with its role as a potent alpha 2-antagonist over the dose range of 0.2 to 2.0 mg.
Assuntos
Antagonistas Adrenérgicos alfa/farmacologia , Clonidina/antagonistas & inibidores , Quinolizinas/farmacologia , Adulto , Glicemia , Pressão Sanguínea/efeitos dos fármacos , Clonidina/administração & dosagem , Método Duplo-Cego , Gonadotropinas/sangue , Frequência Cardíaca/efeitos dos fármacos , Humanos , Infusões Intravenosas , Masculino , Distribuição Aleatória , Salivação/efeitos dos fármacosRESUMO
Conditioned medium was collected from vascular smooth-muscle cells grown in culture to determine if these cells synthesize vasoactive substances. The medium caused a short-acting endothelium-independent constriction of rat aorta, followed by a prolonged, endothelium-dependent relaxation. This relaxation was mediated through the release of endothelium-derived relaxing factor (EDRF) as it was abolished by the addition of methylene blue (5 x 10(-6) M), haemoglobin (10(-6) M) or methyl arginine, but was not affected by indomethacin (10(-5) M). Smooth-muscle medium stimulated the production of EDRF from both rat and rabbit thoracic aortic rings as well as from cultured bovine pulmonary artery endothelial cells. The prolonged stimulation of EDRF by smooth-muscle medium was not mimicked by known physiological stimuli to EDRF release; EDRF-stimulating activity was not affected when smooth-muscle cells were grown in the presence of indomethacin (10(-5) M), although serum in the medium was required. The EDRF-stimulating substance(s) in the smooth-muscle medium was heat stable and associated with a high molecular mass (30,000 greater than Mr greater than 3500) water-soluble species that is as yet unidentified.
Assuntos
Endotélio Vascular/fisiologia , Músculo Liso Vascular/fisiologia , Óxido Nítrico/metabolismo , Animais , Aorta/citologia , Aorta/efeitos dos fármacos , Aorta/fisiologia , Células Cultivadas , Endotélio Vascular/citologia , Técnicas In Vitro , Indometacina/farmacologia , Cinética , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Fenilefrina/farmacologia , Coelhos , Ratos , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
The daily administration of 240 to 360 mg of diltiazem lowered blood pressure in a dose-related pattern similar to that seen in patients taking a daily dosage of 50 to 100 mg of atenolol. Sustained-release diltiazem was administered twice daily and atenolol once. Goal blood pressure was defined as less than 90 mm Hg or a reduction of greater than or equal to 10 mm Hg for patients with baseline pressures of 95 to 99 mm Hg in the supine position and was achieved in 60% of diltiazem-treated and 63% of atenolol-treated patients. The mean diltiazem dosage at the end of the study was 329 mg daily; for atenolol it was 80 mg daily. Adverse reactions considered possibly or probably drug related were reported by 26% of diltiazem patients and 38% of atenolol patients. Although both drugs were associated with a slower heart rate, atenolol patients showed a significantly greater negative chronotropic effect. Diltiazem, in a sustained-release form taken twice daily, is as effective as atenolol as a sole antihypertensive agent. It has a favorable side-effect profile and may be a useful alternative antihypertensive medication compared with existing beta-blocker therapy with atenolol.
Assuntos
Atenolol/uso terapêutico , Diltiazem/administração & dosagem , Hipertensão/tratamento farmacológico , Atenolol/efeitos adversos , Pressão Sanguínea , Ensaios Clínicos como Assunto , Preparações de Ação Retardada , Diltiazem/efeitos adversos , Diltiazem/uso terapêutico , Método Duplo-Cego , Eletrocardiografia , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Distribuição AleatóriaRESUMO
1. The importance of adenylate cyclase-mediated vascular relaxation in the macro and microcirculation was assessed in rabbit aortic and coeliac artery bioassay rings in vitro and skin microvessels in vivo. 2. The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP38), the beta-agonist, isoprenaline, and the prostaglandins, PGE1 and PGE2, were compared with the activity of nitroprusside, which acts by stimulating guanylate cyclase. 3. In aortic tissue the relative relaxant potencies were (-log M EC50, 100% = response to nitroprusside 10(-6) M): nitroprusside 7.0, PACAP38 6.8, isoprenaline 6.3; PGE1 and PGE2 were weak constrictors. In coeliac artery rings relative potencies were (-log M EC50, 100% = response to nitroprusside 10(-5) M): PACAP38 6.6, PGE1 6.6, nitroprusside 6.5, PGE2 4.9, and isoprenaline 4.3. 4. Comparative potencies when injected into anaesthetized rabbit skin in vivo were (-log mol/site required to increase blood red cell flux by 75%): PACAP38 13.0, PGE2 10.7, isoprenaline 9.7, PGE1 9.1, nitroprusside < 7. 5. Nitroprusside, the most effective relaxant tested in the aorta, was 10(7) fold less potent than PACAP in its effect on skin blood flow. PGE1 and PGE2 were constrictors of the aorta, of intermediate effect in the coeliac artery, but potent vasodilators of the microcirculation. 6. In this model, the importance of adenylate cyclase-mediated vascular relaxation increases with decreasing vessel size.
Assuntos
Adenilil Ciclases/fisiologia , Músculo Liso Vascular/fisiologia , Pele/irrigação sanguínea , Animais , Aorta Torácica/fisiologia , Artéria Celíaca/efeitos dos fármacos , Células Cultivadas , AMP Cíclico/metabolismo , Isoproterenol/farmacologia , Masculino , Artérias Mesentéricas/fisiologia , Microcirculação/fisiologia , Neuropeptídeos/farmacologia , Neurotransmissores/farmacologia , Nitroprussiato/farmacologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Prostaglandinas E/farmacologia , Coelhos , Vasodilatadores/farmacologiaRESUMO
1. We have shown previously that exposing the rat or rabbit microcirculation to nifedipine increases the permeability of the post-capillary venule, the segment of microcirculation that is known to control inflammatory oedema. 2. In the present study modulation by the inotropes isoprenaline, dopexamine and dobutamine of nifedipine-induced oedema was examined in the rabbit skin microcirculation by measuring the localised leakage of 125I-radiolabelled albumin after the i.d. injection of agents. 3. Coinjection of isoprenaline (10(-11) moles per site), dopexamine (10(-10) moles per site) or dobutamine (10(-10) moles per site) suppressed significantly (P < 0.05) the oedema response to nifedipine (10(-7.2) moles per site) in the rabbit dorsal skin microcirculation. 4. To confirm the oedema suppresser effect of the inotropes, dopexamine or dobutamine were also coinjected with histamine 10(-8) + PGE2 10(-10) moles per site, or bradykinin 10(-10) + PGE2 10(-10) moles per site. Both inotropes at 10(-10) moles per site reduced significantly (P < 0.05) the leakage of albumin caused by bradykinin + PGE2 and histamine + PGE2. 5. When measured by laser Doppler, basal local skin blood flow increased at 30 min by 57 +/- 14% with nifedipine 10(-7.2) moles per site and 15 +/- 11% with isoprenaline 10(-11) moles per site. Isoprenaline did not suppress the blood flow response to nifedipine, the response to coinjection being 68 +/- 11%. 6. Oedema caused by nifedipine can be suppressed by low concentrations of beta-adrenergic agonists that do not suppress the blood flow response to nifedipine. This suggests that cardiac inotropes can influence non-inflammatory changes in microvascular permeability.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Cardiotônicos/farmacologia , Edema/prevenção & controle , Nifedipino/farmacologia , Pele/efeitos dos fármacos , Animais , Bradicinina/farmacologia , Dinoprostona/farmacologia , Dobutamina/farmacologia , Dopamina/análogos & derivados , Dopamina/farmacologia , Edema/induzido quimicamente , Histamina/farmacologia , Isoproterenol/farmacologia , Masculino , Microcirculação/efeitos dos fármacos , Nifedipino/antagonistas & inibidores , Coelhos , Pele/irrigação sanguíneaRESUMO
1. The role of nitric oxide synthase and cyclo-oxygenase in the skin blood flow response to ultraviolet light B (u.v.B) irradiation was investigated in the rat in vivo. 2. Local skin blood flow changes were measured in the shaved dorsal skin of anaesthetized male Sprague-Dawley rats with a laser Doppler flow probe. 3. u.v.B irradiation caused delayed onset vasodilation and by 18 h basal blood flow increased by 125 +/- 25% (P < 0.05, n = 12 rats, mean +/- s.e. mean). 4. Indomethacin, 3 nmol per site, NG-nitro-L-arginine methyl ester (L-NAME) 100 nmol per site, but not D-NAME 100 nmol per site, injected locally 17.5 h after u.v.B irradiation abolished the 18 h increase in blood flow. 5. The nitric oxide synthase inhibitor L-NAME, NG-monomethyl-L-arginine (L-NMMA) and canavanine, 10 and 100 nmol per site injected at 17.5 h, suppressed significantly the u.v.B 18 h response in a dose-dependent manner. The order of potency was L-NAME > canavanine = L-NMMA. The effect of L-NAME was reversed partially by the co-injection of an excess of L-arginine. 6. Topical application of the corticosteroid, clobetasol 17-propionate, immediately after irradiation inhibited the 18 h u.v.B response in a dose-dependent manner. 7. The delayed onset microcirculatory vasodilation induced by u.v.B involves both nitric oxide synthase and cyclo-oxygenase in this in vivo model. Topical corticosteroids may attenuate the response by inhibiting both prostaglandin and nitric oxide synthesis pathways.
Assuntos
Aminoácido Oxirredutases/fisiologia , Pele/irrigação sanguínea , Vasodilatação/efeitos da radiação , Aminoácido Oxirredutases/antagonistas & inibidores , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Canavanina/farmacologia , Clobetasol/análogos & derivados , Clobetasol/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Indometacina/farmacologia , Fluxometria por Laser-Doppler , Masculino , NG-Nitroarginina Metil Éster , Óxido Nítrico Sintase , Ratos , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional/fisiologia , Fluxo Sanguíneo Regional/efeitos da radiação , Raios Ultravioleta , ômega-N-MetilargininaRESUMO
1. The effect of intradermally injected endotoxin on skin blood flow was investigated in anaesthetized male Wistar rats in vivo. 2. Local skin blood flow changes were measured hourly for 6 h in the shaved dorsal skin with a laser-Doppler flow probe and compared to changes in control sites which had been injected with 100 microliters of phosphate-buffered saline. By 3 h, skin blood flow increased above basal by 129 +/- 27% and 186 +/- 29% with 1 and 10 micrograms of endotoxin respectively. Blood flow remained significantly elevated at 6 h, the corresponding figures being 129 +/- 24% and 154 +/- 31% (P less than 0.05, n = 6 rats, mean +/- s.e.mean). 3. In further experiments, the response to 3 micrograms of endotoxin was measured at 4 h and treatment with a cyclo-oxygenase inhibitor, nitric oxide synthase inhibitors or a topical steroid all significantly inhibited this response (P less than 0.05 in each case, n = 6 rats in each group with duplicate sites in each animal). 4. Indomethacin 3 x 10(-9) mol per site injected 3.5 h after injection of endotoxin suppressed the mean 4 h response to endotoxin by 78%; NG-nitro-L-arginine methyl ester (L-NAME) 10(-7) mol per site suppressed the response by 95%; NG-monomethyl-L-arginine (L-NMMA) 10(-7) mol per site suppressed the response by 50%; whereas the D-isomer of NG-monomethyl-arginine 10(-7) mol per site had no significant effect.5. Topical application of the corticosteroid, betamethasone 17-valerate (1% solution) 18 h before injection of endotoxin inhibited the mean 4 h response to endotoxin by 66% and the 6 h response by 48%.6. In the same model, the vasodilator response to arachidonic acid was inhibited by both indomethacin and nitric oxide synthase inhibitors (P<0.05 in each case).7. These data suggest that the microcirculatory vasodilator response to endotoxin and arachidonic acid injected locally involves both nitric oxide synthase and cyclo-oxygenase in this in vivo model.
Assuntos
Endotoxinas/farmacologia , Óxido Nítrico/metabolismo , Prostaglandinas/biossíntese , Pele/irrigação sanguínea , Vasodilatação/efeitos dos fármacos , Aminoácido Oxirredutases/antagonistas & inibidores , Animais , Técnicas In Vitro , Indometacina/farmacologia , Masculino , Óxido Nítrico Sintase , Ratos , Ratos Endogâmicos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Pele/efeitos dos fármacosRESUMO
1. A new model of tolerance to the hypotensive effect of organic nitrates has been developed in the rat. 2. The fall in mean arterial pressure (MAP) in response to bolus doses of sodium nitroprusside (NP) (4 micrograms kg-1) and glyceryl trinitrate (GTN) (10 micrograms kg-1) was recorded both before and after a 60 min infusion of either 0.9% saline, NP (20 micrograms kg-1 min-1) or GTN (40 micrograms kg-1 min-1). 3. The hypotensive effects of NP or GTN were unchanged following saline infusion, but were reduced in both cases by approximately 40% following the infusion of NP. 4. Infusion of GTN for 60 min virtually abolished the hypotensive effect of a GTN bolus (i.e. nitrate tolerance), whilst the effect of a NP bolus was reduced only to a similar extent (30%) as after an infusion of NP. This latter effect is attributed to a degree of non-specific cross-tolerance between GTN and NP. 5. Co-treatment of a group of rats with N-acetyl-L-cysteine (L-NAC) prevented the development of nitrate tolerance, confirming the role of thiols in this phenomenon, whereas N-acetyl-D-cysteine (D-NAC) did not. 6. The stereospecificity in the effect of NAC in preventing this specific tolerance to GTN suggests that the interaction between GTN and NAC and/or cysteine involves an enzyme-dependent step. 7. NAC was unable to prevent the non-specific cross-tolerance to NP which followed infusion of GTN, suggesting that the mechanism does not directly involve NAC and/or cysteine.
Assuntos
Acetilcisteína/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Nitroglicerina/farmacologia , Animais , Tolerância a Medicamentos , Masculino , Nitroprussiato/farmacologia , Ratos , Ratos Endogâmicos , EstereoisomerismoRESUMO
1 Bradykinin was infused intravenously into conscious rabbits to determine its effect on the concentration of prostaglandins in plasma. 6-Oxo-prostaglandin (PG) F1 alpha, the stable hydrolysis product of prostacyclin, and 13,14-dihydro-15-oxo-PGF2 alpha, a metabolite derived from PGE2 and PGF2 alpha, were measured by gas chromatography-electron capture mass spectrometry. 2 Incremental infusions of bradykinin (0.4-3.2 micrograms kg-1 min-1) increased plasma concentrations of both 6-oxo-PGF1 alpha and 13,14-dihydro-15-oxo-PGF2 alpha. 3 Aspirin (10 mg kg-1, i.v.) inhibited bradykinin-stimulated 6-oxo-PGF1 alpha and 13,14-dihydro-15-oxo-PGF2 alpha synthesis at 30 min and 6 h. At 24 h, the mean bradykinin-stimulated 13,14-dihydro-15-oxo-PGF2 alpha concentration was 66% of its original value, whilst 6-oxo-PGF1 alpha remained substantially inhibited. 4 The different rates of recovery of bradykinin-stimulated production of the two prostaglandins after inhibition by aspirin suggests that intravenous bradykinin stimulates prostacyclin and PGE2/PGF2 alpha production in distinct cell populations which synthesize cyclo-oxygenase at different rates.
Assuntos
Bradicinina/farmacologia , Dinoprosta/análogos & derivados , Prostaglandinas/biossíntese , Animais , Aspirina/farmacologia , Masculino , Prostaglandinas/sangue , Prostaglandinas F/farmacologia , CoelhosRESUMO
1. The effects of pituitary adenylate cyclase activating polypeptide (PACAP) on microvascular blood flow and plasma protein leakage were investigated in rabbit skin in vivo. 2. Intradermal injection of PACAP38, the 38 amino acid form of the peptide, caused a dose-dependent increase in blood flow measured by a 133Xe clearance technique. An equivalent increase in blood flow was induced by 10(-12) mol per site of PACAP38, 10(-12) mol per site of human alpha-calcitonin gene-related peptide (CGRP) and 10(-10) mol per site of vasoactive intestinal polypeptide (VIP). 3. The vasodilator activity of PACAP38 was not significantly different from that of the 27 amino acid form of the peptide, PACAP27, when measured with a laser Doppler flow meter, causing a 104 +/- 14% compared with 110 +/- 18% increase above basal blood flow at 10(-12) mol per site respectively. 4. At 10(-12) mol per site the effect of PACAP38 was longer lasting than that of CGRP. Blood flow remained significantly increased above control at 2 h with PACAP38 (P less than 0.05) whereas blood flow after intradermal CGRP had returned to control values by this time. 5. PACAP38 injected alone had no significant effect on microvascular leakage of 125I-labelled albumin. However, PACAP38 significantly potentiated bradykinin-induced oedema where it was approximately 100 fold more potent than VIP. 6. Oedema potentiation induced by PACAP38 was not inhibited by indomethacin at a dose which did inhibit potentiation of bradykinin-induced oedema by arachidonic acid.7. PACAP38 is at least as potent as other peptides which have been postulated to be involved in the inflammatory response when tested in rabbit skin in vivo. PACAP may contribute to both the hyperaemia and oedema components of inflammation.
Assuntos
Edema/induzido quimicamente , Neuropeptídeos/farmacologia , Vasodilatadores/farmacologia , Animais , Bradicinina , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Sinergismo Farmacológico , Edema/fisiopatologia , Indometacina/farmacologia , Radioisótopos do Iodo , Masculino , Microcirculação/efeitos dos fármacos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Coelhos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fluxo Sanguíneo Regional/fisiologia , Pele/irrigação sanguínea , Radioisótopos de XenônioRESUMO
Mechanical work rate of breathing was measured in five normal subjects during voluntary eucapnic hyperventilation at rates of approximately 10, 20, 40, 60, and 80 l/min before and after inhalation of 1 mg of ipratropium bromide, an anticholinergic agent. Chest wall recoil pressure was measured over a range of lung volumes in each subject and was used as the reference pressure in the calculation of work rate. There was little change in elastic or resistive work rate at rest when vagal tone was reduced by ipratropium. The mean work at 40, 60, and 80 l/min was 8.9, 17.2, and 34.0 cmH2O.l-1.s before and 5.6, 12.4 and 25.8 cmH2O.l-1.s after ipratropium. This suggests that vagal tone significantly influences the work of breathing at high ventilatory rates, such as occur during strenuous exercise.