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1.
Public Health ; 182: 19-25, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32120067

RESUMO

OBJECTIVES: To describe a cross-border foodborne outbreak of Shigella sonnei that occurred in Ireland and Northern Ireland (NI) in December 2016 whilst also highlighting the valuable roles of sales data and international collaboration in the investigation and control of this outbreak. STUDY DESIGN: A cross-border outbreak control team was established to investigate the outbreak. METHODS: Epidemiological, microbiological, and environmental investigations were undertaken. Traditional analytical epidemiological studies were not feasible in this investigation. The restaurant chain provided sales data, which allowed assessment of a possible increased risk of illness associated with exposure to a particular type of heated food product (product A). RESULTS: Confirmed cases demonstrated sole trimethoprim resistance: an atypical antibiogram for Shigella isolates in Ireland. Early communication and the sharing of information within the outbreak control team facilitated the early detection of the international dimension of this outbreak. A joint international alert using the European Centre for Disease Control's confidential Epidemic Intelligence Information System for Food- and Waterborne Diseases and Zoonoses (EPIS-FWD) did not reveal further cases outside of the island of Ireland. The outbreak investigation identified that nine of thirteen primary case individuals had consumed product A from one of multiple branches of a restaurant chain located throughout the island of Ireland. Product A was made specifically for this chain in a food production facility in NI. S. sonnei was not detected in food samples from the food production facility. Strong statistical associations were observed between visiting a branch of this restaurant chain between 5 and 9 December 2016 and eating product A and developing shigellosis. CONCLUSIONS: This outbreak investigation highlights the importance of international collaboration in the efficient identification of cross-border foodborne outbreaks and the value of using sales data as the analytical component of such studies.


Assuntos
Surtos de Doenças/estatística & dados numéricos , Disenteria Bacilar/epidemiologia , Doenças Transmitidas por Alimentos/epidemiologia , Shigella sonnei , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Comércio/economia , Surtos de Doenças/economia , Disenteria Bacilar/economia , Disenteria Bacilar/microbiologia , Feminino , Microbiologia de Alimentos , Doenças Transmitidas por Alimentos/economia , Doenças Transmitidas por Alimentos/microbiologia , Humanos , Irlanda/epidemiologia , Masculino , Pessoa de Meia-Idade , Irlanda do Norte/epidemiologia , Restaurantes , Adulto Jovem
2.
Medchemcomm ; 8(6): 1255-1267, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30108836

RESUMO

In this article, we describe the discovery of an aryl ether series of potent and selective Nav1.3 inhibitors. Based on structural analogy to a similar series of compounds we have previously shown bind to the domain IV voltage sensor region of Nav channels, we propose this series binds in the same location. We describe the development of this series from a published starting point, highlighting key selectivity and potency data, and several studies designed to validate Nav1.3 as a target for pain.

3.
J Pharmacol Exp Ther ; 298(2): 718-28, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11454936

RESUMO

The effects of the cytochrome P450 inhibitors clotrimazole, ketoconazole, and 1-aminobenzotriazole (1-ABT) on native delayed rectifier (K(DR)) and cloned Kv1.5 (RPV Kv1.5) K+ channels of rabbit portal vein (RPV) myocytes were determined using whole-cell and single channel patch-clamp analysis. Clotrimazole reduced K(DR) and RPV Kv1.5 whole-cell current with respective Kd values of 1.15 +/- 0.39 and 1.99 +/- 0.6 microM. Clotrimazole acted via an open state blocking mechanism based on the following: 1) the early time course of K(DR) current activation was not affected, but inhibition developed with time during depolarizing steps and increased the rate of decay in current amplitude; 2) the inhibition was voltage-dependent, increasing steeply over the voltage range of K(DR) activation; and 3) mean open time of RPV Kv1.5 channels in inside-out patches was decreased significantly. Ketoconazole reduced K(DR) current amplitude with a Kd value of 38 +/- 3.2 microM. However, ketoconazole acted via a closed (resting) state blocking mechanism: 1) K(DR) amplitude was reduced throughout the duration of depolarizing steps and the rate of decay of current was unaffected, 2) there was no voltage dependence to the block by ketoconazole over the K(DR) activation range, and 3) ketoconazole did not affect mean open time of RPV Kv1.5 channels in inside-out membrane patches. 1-ABT between 0.5 and 3 mM did not affect native K(DR) or RPV Kv1.5 current of rabbit portal vein myocytes. Clotrimazole and ketoconazole, but not 1-ABT, suppress vascular K(DR) channels by direct, state-dependent block mechanisms not involving the modulation of cytochrome P450 enzyme activity.


Assuntos
Inibidores das Enzimas do Citocromo P-450 , Inibidores Enzimáticos/farmacologia , Músculo Esquelético/metabolismo , Músculo Liso Vascular/metabolismo , Bloqueadores dos Canais de Potássio , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Canais de Potássio , Algoritmos , Animais , Células Cultivadas , Clotrimazol/farmacologia , Eletrofisiologia , Técnicas In Vitro , Cetoconazol/farmacologia , Canal de Potássio Kv1.5 , Músculo Esquelético/citologia , Músculo Esquelético/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Técnicas de Patch-Clamp , Coelhos , Transfecção
7.
Br J Pharmacol ; 128(3): 653-8, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10516645

RESUMO

1. Acetycholine-mediated relaxations in phenylephrine-contracted aortas, femoral and mesenteric resistance arteries were studied in vessels from endothelial nitric oxide synthase knock-out (eNOS -/-) and the corresponding wild-type strain (eNOS +/+) C57BL6/SV19 mice. 2. Aortas from eNOS (+/+) mice relaxed to acetylcholine in an endothelium-dependent NG-nitro-L-arginine (L-NOARG) sensitive manner. Aortas from eNOS (-/-) mice did not relax to acetylcholine but demonstrated enhanced sensitivity to both authentic NO and sodium nitroprusside. 3. Relaxation to acetylcholine in femoral arteries was partially inhibited by L-NOARG in vessels from eNOS (+/+) mice, but relaxation in eNOS (-/-) mice was insensitive to a combination of L-NOARG and indomethacin and the guanylyl cyclase inhibitor 1H-[1,2, 4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). The L-NOARG/ODQ/indomethacin-insensitive relaxation to acetylcholine in femoral arteries was inhibited in the presence of elevated (30 mM) extracellular KCl. 4. In mesenteric resistance vessels from eNOS (+/+) mice, the acetylcholine-mediated relaxation response was completely inhibited by a combination of indomethacin and L-NOARG or by 30 mM KCl alone. In contrast, in mesenteric arteries from eNOS (-/-) mice, the acetylcholine-relaxation response was insensitive to a combination of L-NOARG and indomethacin, but was inhibited in the presence of 30 mM KCl. 5. These data indicate arteries from eNOS (-/-) mice demonstrate a supersensitivity to exogenous NO, and that acetylcholine-induced vasorelaxation of femoral and mesenteric vessels from eNOS (-/-) mice is mediated by an endothelium-derived factor that has properties of an EDHF but is neither NO nor prostacyclin. Furthermore, in mesenteric vessels, there is an upregulation of the role of EDHF in the absence of NO.


Assuntos
Acetilcolina/farmacologia , Artérias/efeitos dos fármacos , Óxido Nítrico Sintase/genética , Animais , Artérias/enzimologia , Artérias/fisiologia , Fatores Biológicos/fisiologia , Inibidores Enzimáticos/farmacologia , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Relaxamento Muscular/efeitos dos fármacos , Óxido Nítrico/farmacologia , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II , Óxido Nítrico Sintase Tipo III , Nitroarginina/farmacologia , Nitroprussiato/farmacologia
9.
Clin Exp Pharmacol Physiol ; 26(2): 176-9, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10065343

RESUMO

1. Endothelium-derived relaxing factor is almost universally considered to be synonymous with nitric oxide (NO); however, it is now well established that at least two other chemically distinct species (prostacyclin (PGI2) and a hyperpolarizing factor) may also contribute to endothelium-dependent relaxation. 2. Only relatively few studies have provided definitive evidence that an endothelium-derived hyperpolarizing factor (EDHF), which is neither NO nor PGI2, exists as a chemical mediator. 3. There is a lack of agreement as to the likely chemical identity of this putative factor. Some evidence suggests that EDHF may be a cytochrome P450-derived arachidonic acid product, possibly an epoxyeicosatrienoic acid (EET); conflicting evidence supports an endogenous cannabinoid as the mediator and still other studies infer an unknown mediator that is neither a cytochrome P450 nor a cannabinoid. 4. Data from our laboratory with a rabbit carotid artery 'sandwich' preparation have provided evidence that a mediator that meets the pharmacological expectations of a cytochrome P450 product is an EDHF. 5. Data from guinea-pig mesenteric arterioles suggest that EDHF is not a cytochrome P450 product, whereas in guinea-pig middle cerebral arteries, relaxation mediated by the NO/PGI2-independent mediator(s) is sensitive to cytochrome P450 inhibitors. In addition, in the rabbit middle cerebral artery, it is likely that endothelium-dependent hyperpolarization is mediated by both NO and PGI2. 6. In conclusion, these data indicate that EDHF is unlikely to be a single factor and that considerable tissue and species differences exist for the nature and cellular targets of the hyperpolarizing factors.


Assuntos
Fatores Biológicos/metabolismo , Artérias Carótidas/metabolismo , Artérias Cerebrais/metabolismo , Artérias Mesentéricas/metabolismo , Animais , Epoprostenol/metabolismo , Cobaias , Óxido Nítrico/metabolismo , Coelhos , Especificidade da Espécie , Distribuição Tecidual
10.
Clin Exp Pharmacol Physiol ; 26(2): 180-4, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10065344

RESUMO

1. Endothelium-derived relaxing factors (EDRF), including nitric oxide (NO), prostacyclin (PGI2) and an as yet uncharacterized endothelium-derived hyperpolarizing factor (EDHF), are now recognized to induce relaxation of vascular smooth muscle, in part via the activation of K+ channels. 2. Experiments using selective K+ channel blockers, including iberiotoxin (IbTX), glibenclamide, apamin and 4-aminopyridine (4-AP) to inhibit endothelium-induced relaxation suggest that more than one type of K+ channel may be involved, depending on the species and tissue, including: (i) large conductance Ca(2+)-activated (BKCa) channels; (ii) ATP-sensitive (KATP) channels; (iii) small conductance Ca(2+)-activated (SKCa) channels; and (iv) voltage-gated (Kv) K+ channels. 3. Recent observations suggest a role for Kv channels in some vessels based on a sensitivity of NO- and PGI2-mediated relaxations to 4-AP, as well as a complete suppression of EDHF-dependent relaxation by a combination of charybdotoxin (ChTX) and apamin but not IbTX and apamin. 4. The molecular identity of the K+ channels affected by EDRF is not well characterized. Recently, findings indicate that the pore-forming alpha-subunit tetramers of vascular smooth muscle BKCa channels are due to the expression of the so-called Slo channel gene. The identities of the KATP, SKCa and Kv channels involved in endothelium-dependent vasodilation are not known. 5. The component of whole-cell Kv current affected by PGI2 may be due to slowly inactivating, 4-AP-sensitive, 15 pS delayed-rectifier K+ channels (KDR); the activity of these channels in vascular myocytes is increased by forskolin and protein kinase A (PKA) and rabbit portal vein Kv1.5 pore-forming alpha-subunits, which appear to be a component of native KDR current and possess consensus phosphorylation sequences for PKA.


Assuntos
Músculo Liso Vascular/metabolismo , Óxido Nítrico/metabolismo , Canais de Potássio/metabolismo , Animais , Canais Iônicos/metabolismo , Especificidade da Espécie , Distribuição Tecidual , Vasodilatação
11.
Am J Physiol ; 275(2): L336-47, 1998 08.
Artigo em Inglês | MEDLINE | ID: mdl-9700095

RESUMO

The properties of delayed rectifier K+ current [IK(dr)] of canine airway smooth muscle cells isolated from small bronchi and its modulation by protein kinase C (PKC) were studied by whole cell patch clamp. IK(dr) activated positive to -40 mV, with half-maximal activation at -16 +/- 1.2 mV (n = 15) and average current density of 31 +/- 2.6 pA/pF (n = 15) at +30 mV. The capacitive surface area, current density, and voltage dependence of activation of IK(dr) of myocytes of ragweed pollen-sensitized dogs were not different from age-matched control dogs. However, the sensitization reduced the availability of IK(dr) between -40 and -20 mV due to a hyperpolarizing shift in the voltage dependence of steady-state inactivation (-29.9 +/- 1.2 in sensitized versus -26.0 +/- 0.7 mV in control dogs, n = 9 and 11, respectively; P < 0.05). PKC activation with diacylglycerol analog or phorbol ester depressed IK(dr) amplitude, whereas an inactive diacylglycerol analog had no effect. The hyperpolarizing shift in voltage dependence of inactivation and/or modulation of IK(dr) by PKC may be two mechanisms that contribute to the enhanced reactivity of bronchial tissues from ragweed pollen-sensitized dogs.


Assuntos
Brônquios/fisiologia , Pólen , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Canais de Potássio/fisiologia , Proteína Quinase C/metabolismo , Animais , Animais Recém-Nascidos , Brônquios/imunologia , Cálcio/farmacologia , Células Cultivadas , Quelantes/farmacologia , Canais de Potássio de Retificação Tardia , Cães , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Condutividade Elétrica , Ativação Enzimática , Imunização , Potenciais da Membrana , Técnicas de Patch-Clamp , Dibutirato de 12,13-Forbol/farmacologia , Tetraetilamônio/farmacologia
12.
Br J Pharmacol ; 123(5): 821-32, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9535009

RESUMO

1. The cellular mechanism(s) of action of endothelium-derived vasodilator substances in the rabbit middle cerebral artery (RMCA) were investigated. Specifically, the subtypes of potassium channels involved in the effects of endothelium-derived relaxing factors (EDRFs) in acetylcholine (ACh)-induced endothelium-dependent vasorelaxation in this vessel were systematically compared. 2. In the endothelium-intact RMCA precontracted with histamine (3 microM), ACh induced a concentration-dependent vasorelaxation, which was sensitive to indomethacin (10 microM) or N(G)-nitro-L-arginine (L-NOARG; 100 microM); pD2 values 8.36 vs 7.40 and 6.38, P < 0.01 for both, n = 6 and abolished by a combination of both agents. ACh caused relaxation in the presence of high K+ PSS (40 mM KCl), which was not affected by indomethacin, but abolished by L-NOARG and a combination of indomethacin and L-NOARG. 3. In the presence of indomethacin, relaxation to ACh in the endothelium-intact RMCA precontracted with histamine was unaffected by either glibenclamide (10 microM), an ATP-sensitive K+ channel (K[ATP]) blocker, 4-aminopyridine (4-AP, 1 mM) or dendrotoxin (DTX, 0.1 microM), delayed rectifier K channel (Kv) blockers. However, relaxation responses to ACh were significantly inhibited by either LY83583 (10 microM) and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 10 microM), guanylyl cyclase inhibitors, or charybdotoxin (CTX; 0.1 microM), iberiotoxin (ITX, 0.1 microM) and apamin (APA, 0.1 microM), large conductance Ca2+-activated K+ channels (BK[Ca]) blocker and small conductance Ca2+-activated K+ channel (SK[Ca]) blocker, respectively. 4. In the presence of L-NOARG, relaxation to ACh was unaffected by glibenclamide or the cytochrome P450 mono-oxygenase inhibitor, clotrimazole (1 microM), but was significantly inhibited by either 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22,536, 10 microM) and 2',3'-dideoxyadenosine (2',3'-DDA, 30 microM), adenylyl cyclase inhibitors, or 4-AP, DTX, CTX, ITX and APA. 5. In the endothelium-denuded RMCA precontracted with histamine, authentic NO-induced relaxation was unaffected by glibenclamide, 4-AP and DTX, but significantly reduced by ODQ, ITX and APA. Authentic prostaglandin I2 (PGI2)-induced relaxation was unaffected by glibenclamide, but significantly reduced by 2',3'-DDA, 4-AP, DTX, ITX and APA. Forskolin-induced relaxation was significantly inhibited by high K+, CTX and 4-AP. 6. These results indicate that: (1) in the RMCA the EDRFs released by ACh are NO and a prostanoid (presumably PGI2), and there is no evidence for the release of a non-NO/PGI2 endothelium-derived hyperpolarizing factor (EDHF), (2) K(Ca) channels are involved in NO-mediated relaxation of the RMCA but both K(Ca) and Kv channels are involved in PGI2-mediated relaxation.


Assuntos
Cálcio/metabolismo , Artérias Cerebrais/fisiologia , Endotélio Vascular/fisiologia , Ativação do Canal Iônico , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Canais de Potássio/fisiologia , Acetilcolina/metabolismo , Animais , Artérias Cerebrais/efeitos dos fármacos , Canais de Potássio de Retificação Tardia , Endotélio Vascular/efeitos dos fármacos , Técnicas In Vitro , Masculino , Relaxamento Muscular/efeitos dos fármacos , Relaxamento Muscular/fisiologia , Óxido Nítrico/fisiologia , Prostaglandinas/fisiologia , Coelhos
13.
Br J Pharmacol ; 121(8): 1509-11, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9283682

RESUMO

The endogenous cannabinoid, anandamide, has been suggested as an endothelium-derived hyperpolarizing factor (EDHF). We found that anandamide-evoked relaxation in isolated segments of rat mesenteric artery was associated with smooth muscle hyperpolarization. However, although anandamide-evoked relaxation was inhibited by either charybdotoxin (ChTX) or iberiotoxin, inhibition of the relaxation to EDHF required a combination of ChTX and apamin. The relaxations induced by either anandamide or EDHF were not inhibited by the cannabinoid receptor (CB1) antagonist SRI41716A, or mimicked by selective CB1 agonists. Thus, anandamide appears to cause smooth muscle relaxation via a CB1 receptor-independent mechanism and cannabinoid receptor activation apparently does not contribute to EDHF-mediated relaxation in this resistance artery.


Assuntos
Ácidos Araquidônicos/farmacologia , Fatores Biológicos/fisiologia , Canabinoides/farmacologia , Artérias Mesentéricas/efeitos dos fármacos , Animais , Apamina/farmacologia , Relação Dose-Resposta a Droga , Endocanabinoides , Técnicas In Vitro , Masculino , Artérias Mesentéricas/fisiologia , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas , Pirazóis/farmacologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Receptores de Canabinoides , Receptores de Droga/efeitos dos fármacos , Rimonabanto , Vasodilatação/efeitos dos fármacos
14.
Br J Pharmacol ; 120(4): 695-701, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9051310

RESUMO

1. The nature and cellular mechanisms that are responsible for endothelium-dependent relaxations resistant to indomethacin and NG-nitro-L-arginine methyl ester (L-NAME) were investigated in phenylephrine (PE) precontracted isolated carotid arteries from the rabbit. 2. In the presence of the cyclo-oxygenase inhibitor, indomethacin (10 microM), acetylcholine (ACh) induced a concentration- and endothelium-dependent relaxation of PE-induced tone which was more potent than the calcium ionophore A23187 with pD2 values of 7.03 +/- 0.12 (n = 8) and 6.37 +/- 0.12 (n = 6), respectively. The ACh-induced response was abolished by removal of the endothelium, but was not altered when indomethacin was omitted (pD2 value 7.00 +/- 0.10 and maximal relaxation 99 +/- 3%, n = 6). Bradykinin and histamine (0.01-100 microM) had no effect either upon resting or PE-induced tone (n = 5). 3. In the presence of indomethacin plus the NO synthase inhibitor, L-NAME (30 microM), the response to A23187 was abolished. However, the response to ACh was not abolished, although it was significantly inhibited with the pD2 value and the maximal relaxation decreasing to 6.48 +/- 0.10 and 67 +/- 3%, respectively (for both P < 0.01, n = 8). The L-NAME/indomethacin insensitive vasorelaxation to ACh was completely abolished by preconstriction of the tissues with potassium chloride (40 mM, n = 8). 4. The Ca(2+)-activated K+ (KCa) channel blockers, tetrabutylammonium (TBA, 1 mM, n = 5) and charybdotoxin (CTX, 0.1 microM, n = 5), completely inhibited the nitric oxide (NO) and prostacyclin (PGI2)-independent relaxation response to ACh. However, iberiotoxin (ITX, 0.1 microM, n = 8) or apamin (1-3 microM, n = 6) only partially inhibited the relaxation. 5. Inhibitors of the cytochrome P450 mono-oxygenase, SKF-525A (1-10 microM, n = 6), clotrimazole (1 microM, n = 5) and 17-octadecynoic acid (17-ODYA, 3 microM, n = 7) also reduced the NO/PGI2-independent relaxation response to ACh. 6. In endothelium-denuded rings of rabbit carotid arteries, the relaxation response to exogenous NO was not altered by either KCa channel blockade with apamin (1 microM, n = 5) or CTX (0.1 microM, n = 5), or by the cytochrome P450 mono-oxygenase blockers SKF-525A (10 microM, n = 4) and clotrimazole (10 microM, n = 5). However, the NO-induced response was shifted to the right by LY83583 (10 microM, n = 4), a guanylyl cyclase inhibitor, with the pD2 value decreasing from 6.95 +/- 0.14 to 6.04 +/- 0.09 (P < 0.01). 7. ACh (0.01-100 microM) induced a concentration-dependent relaxation of PE-induced tone in endothelium-denuded arterial segments sandwiched with endothelium-intact donor segments. This relaxation to ACh was largely unaffected by indomathacin (10 microM) plus L-NAME (30 microM), but abolished by the combination of indomethacin, L-NAME and TBA (1 mM, n = 5). 8. These data suggest that in the rabbit carotid artery: (a) ACh can induce the release of both NO and EDHF, whereas A23187 only evokes the release of NO from the endothelium, (b) the diffusible EDHF released by ACh may be a cytochrome P450-derived arachidonic acid metabolite, and (c) EDHF-induced relaxation involves the opening of at least two types of KCa channels, whereas NO mediates vasorelaxation via a guanosine 3': 5'-cyclic monophosphate (cyclic GMP)-mediated pathway, in which a cytochrome P450 pathway and KCa channels do not seem to be involved.


Assuntos
Fatores Biológicos/metabolismo , Inibidores das Enzimas do Citocromo P-450 , Endotélio Vascular/fisiologia , Músculo Liso Vascular/fisiologia , Bloqueadores dos Canais de Potássio , Vasodilatação , Acetilcolina , Animais , Apamina/farmacologia , Artérias Carótidas/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Epoprostenol/farmacologia , Feminino , Técnicas In Vitro , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Óxido Nítrico/farmacologia , Proadifeno/farmacologia , Coelhos , Vasodilatação/efeitos dos fármacos
15.
Eur J Pharmacol ; 318(1): 89-92, 1996 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-9007517

RESUMO

The presence of functional endothelin ETB receptors was investigated in rat isolated mesenteric resistance arteries. Neither endothelin-3 (0.1-100 nM) nor the endothelin ETB selective agonists sarafotoxin S6c and BQ 3020 (both 1-100 nM) induced any measurable hyperpolarization or relaxation in stimulated (alpha 1-adrenoceptor agonist; phenylephrine) or unstimulated arteries. In both cases, the subsequent addition of acetylcholine (1 microM) hyperpolarized the membrane potential by 10-20 mV and totally reversed any contraction which was present. These results indicate that the endothelin ETB-mediated vasodilatation observed in the intact mesenteric bed does not reflect hyperpolarization of smooth muscle cells in resistance arteries arising from the mesenteric artery.


Assuntos
Artérias Mesentéricas/fisiologia , Músculo Liso Vascular/fisiologia , Receptores de Endotelina/fisiologia , Animais , Endotelina-3/farmacologia , Endotelinas/farmacologia , Masculino , Potenciais da Membrana/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Vasoconstritores/farmacologia , Venenos de Víboras/farmacologia
17.
Zhongguo Yao Li Xue Bao ; 17(1): 3-7, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8737442

RESUMO

There is now a considerable evidence that indicates that there is non-NO/prostanoid mediated vasodilation/hyperpolarization mechanism in a variety of blood vessels from different species. It is argued that a factor, EDHF, is responsible for mediating these cellular events and, like NO, EDHF is synthesized and released, in a Ca(2+)-dependent manner, from endothelial cells and activates vascular K+ channel(s) with the predominant evidence suggesting K(Ca) (iberiotoxin and/or apamin sensitive) though this remains to be absolutely confirmed. A number of studies also indicate that a cytochrome P-450 metabolite of arachidonic acid, namely an epoxyeicosatrienoic acid, may serve as the chemical messenger between endothelial and vascular smooth muscle cells. Evidence confirming that there is chemical transmission between endothelial and vascular smooth muscle cells is, however, minimal. Although significant progress has been recently made, much needs to be discovered concerning the nature, synthesis, release, vascular effects as well as the role of EDHF in normal and diseased vascular tissue.


Assuntos
Fatores Biológicos/fisiologia , Endotélio Vascular/metabolismo , Músculo Liso Vascular/metabolismo , Animais , Fatores Biológicos/biossíntese , Músculo Liso Vascular/fisiologia , Óxido Nítrico/fisiologia , Canais de Potássio
18.
Health Bull (Edinb) ; 53(5): 249-52, 1995 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7490194

RESUMO

The Scottish targets for coronary heart disease are examined in detail from the point of view of a Health Board. It is suggested that even though the target refers to the under 65 age group, further age/sex standardisation is needed for fair comparison. A least-squares regression technique is also recommended as a means of reducing the effect of atypical rates in baseline or target years. The targets adopted do not make it clear whether Health Boards should aim for a target in terms of the percentage fall, or should aim to be below an absolute level by the target year. The specific targets imply that resources will have to be concentrated in people of late middle age, particularly males, to the detriment of preventive activities in younger age groups. It seems necessary to emphasise that targets are not an end in themselves but merely an indicator of progress. Monitoring progress towards achieving the target could be achieved by assuming a linear fall in rate between baseline and target years, to produce annual intermediate targets. A health board's progress towards the final target can then be annually monitored by comparison of its regressed age-sex standardised rate with the intermediate target.


Assuntos
Doença das Coronárias/mortalidade , Promoção da Saúde/estatística & dados numéricos , Adulto , Idoso , Causas de Morte , Doença das Coronárias/prevenção & controle , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Escócia
20.
J Public Health Med ; 17(1): 85-9, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7540398

RESUMO

BACKGROUND: Proposals to widen the section of the M25 motorway that passes through East Surrey caused considerable concern and claims that the traffic on the road was responsible for an increasing prevalence of asthma. This study was designed to ascertain the prevalence of asthma-related symptoms among schoolchildren in the District and determine whether there was an association with proximity to a motorway. METHODS: A total of 2387 children aged between 13 and 14 from 17 schools in East Surrey were invited to participate in a survey of the prevalence of asthma-related respiratory symptoms. The survey instrument used was the core asthma questionnaire of the International Survey on Asthma and Allergies in Childhood (ISAAC). The children were grouped according to electoral ward of residence and comparisons were made between urban and rural wards, and the presence or absence of a section of motorway. RESULTS: The prevalence of reported symptoms varied from 2.2 per cent reporting sleep disturbance on more than one night each week to 40 per cent reporting a wheezing episode at some time in their lives; 16 per cent reported a diagnosis of asthma. The overall prevalence of symptoms did not differ greatly from that reported in other similar studies. There was a decrease in the prevalence of asthma-related symptoms in areas close to motorways, which was statistically significant for two questions. This is unlikely to be due to the rural location of the motorways. CONCLUSION: This study suggests that the motorways in East Surrey, in their present configuration, are not responsible for an increased prevalence of respiratory symptoms associated with asthma.


Assuntos
Asma/epidemiologia , Asma/etiologia , Emissões de Veículos , Adolescente , Obstrução das Vias Respiratórias/etiologia , Poluição Ambiental , Feminino , Humanos , Masculino , Prevalência , População Rural , População Urbana
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