RESUMO
INTRODUCTION: Combat readiness assessments through simulated tasks (STs) have been developed for the Brazilian Air Force (BAF) to establish physical employment standards. Previous research has established BAF critical combat tasks with STs developed based on the physical demands of these tasks. Before implementing these STs, the standards required of BAF personnel must be established. The aim of this study was to determine the cut-off scores for five previously established STs. METHODS: Eighty-eight cadets attended three different testing batteries in order to complete the five STs, being: Battery 1 (foot march), Battery 2 (plane crash on water and water survival skills) and Battery 3 (plane crash on land, obstacle course) with their times recorded. Cut-off scores were set at the 85th percentile of the data distribution with these values and then analysed by four subject matter experts (SMEs) using subjective criteria through criterion analysis. RESULTS: All 88 cadets were submitted to the five assessments. After analysing the performance results on the STs, the SMEs discussed and agreed on the following cut-off scores: obstacle course (3:21 min:s), foot march (31:00 min:s), plane crash on land (1:25 min:s), plane crash on water (1:12 min:s) and water survival skills (4:03 min:s). CONCLUSION: The outcomes of this research allow for the five STs to be implemented in BAF cadets and qualified BAF personnel with the established cut-off scores used to monitor the operational capability of these personnel (be it for cadet training outcomes or unit preparedness assessments) and to guide conditioning practices if personnel are below standards.
RESUMO
Tachykinin neuropeptides, such as substance P, are localized to a population of sensory fibers that innervate the mammalian female reproductive tract. In the present study, we have characterized tachykinin NK1 receptor (NK1R), NK2 receptor (NK2R), and NK3 receptor (NK3R) gene expression by semiquantitative RT-PCR in uteri from ovariectomized rats and studied their regulation in response to 17beta-estradiol (E2), progesterone (P4), or a combination of both. In addition, we analyzed the expression and regulation of the neutral endopeptidase 24.11 (NEP), the most important enzyme involved in tachykinin degradation in the rat uterus. In uteri from control (olive oil-treated) rats, RT-PCR assays revealed single bands corresponding to the expected product sizes encoding complementary DNA for NK1R (232 bp), NK2R (491 bp), NK3R (325 bp), and NEP (221 bp). The identity of the amplified fragments was confirmed by DNA sequence analysis. Compared with control rats, NK1R messenger RNA (mRNA) was increased by 2-fold in uteri from rats treated with E2, was decreased by 3.3-fold in rats treated with P4, and was decreased by 1.8-fold in rats treated with both E2 and P4. Uterine NK2R mRNA levels were not altered by any steroid treatment. E2 treatment decreased by 15-fold NK3R mRNA. P4 was without effect if administered alone and did not influence the E2-induced decrease in NK3R mRNA. NEP mRNA levels were about 4-fold lower in E2-treated than in P4-treated rats. Functional studies were carried out in uteri from E2- or P4-treated ovariectomized rats to characterize the contractile response evoked by the selective tachykinin receptor agonists [Sar9Met(O2)11]substance P (NK1R selective), [Nle10]NKA-(4-10) (NK2R selective), and [MePhe7]NKB (NK3R selective) in the presence of the NEP inhibitor phosphoramidon (1 microM). A marked correlation was observed between the magnitude of the contractile response to each agonist and the level of expression determined by RT-PCR for each tachykinin receptor. The present findings show that tachykinin NK1R, NK2R, NK3R, and NEP are expressed in the rat uterus and that ovarian steroids differentially regulate their expression.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Hormônios Esteroides Gonadais/farmacologia , Neprilisina/genética , Receptores de Taquicininas/genética , Útero/metabolismo , Animais , Feminino , RNA Mensageiro/análise , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
1 The aim of our study was to characterize the tachykinin receptor population in the oestrogen-primed rat uterus. For this purpose, we investigated the receptor type(s) responsible for tachykinin-induced contraction of longitudinally-arranged smooth muscle layer. The effects of substance P (SP), neurokinin A (NKA), neurokinin B (NKB) and several of their analogues with well-defined selectivities for tachykinin NK1, NK2 and NK3 receptors were studied and their inhibition by the selective nonpeptide tachykinin receptor antagonists (S)1-(2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)pip eridin-3-yl]ethyl)-4-phenyl- -azoniabicyclo[2.2.2]octane chloride (SR 140333, NK1-selective), (S)-N-methyl-N[4-(4acetylamino-4-phenylpiperidino)-2-(3,4-dichloro phenyl)butyl]benzamide (SR 48968, NK2-selective) and (R)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)prop yl)-4-phenylpiperidin-4-yl)-N- methyla-cetamide (SR 142801, NK3-selective) was evaluated. Additionally, expression of tachykinin receptor mRNA was examined by using the reverse transcription-polymerase chain reaction (RT-PCR). 2 SP, NKA, [Nle10]-NKA(4-10), the analogue with selectivity at the tachykinin NK2 receptor type, and NKB elicited concentration-dependent contractions of the rat uterus. The pD2 values were 5.95+/-0.19; 6.73+/-0.21; 7.53+/-0.12 and 5.76+/-0.21, respectively. The selective agonist for the tachykinin NK1 receptor [Sar9Met(O2)11]-SP produced a small phasic response in the nanomolar concentration range. The selective tachykinin NK3 receptor agonist [MePhe7]-NKB failed to induce any significant contraction. 3 In the presence of the neutral endopeptidase inhibitor phosphoramidon (1 microM), the log concentration-response curves to exogenous tachykinins and their analogues were shifted significantly leftwards. The pD2 values were 6.12+/-0.10, 8.04+/-0.07, 7.89+/-0.03 and 6.59+/-0.07 for SP, NKA, [Nle10]-NKA(4-10) and NKB, respectively. In the presence of phosphoramidon (1 microM), [Sar9Met(O2)11]-SP (1 nM - 0.3 microM) induced concentration-dependent contractions of increasing amplitude when only one concentration of drug was applied to each uterine strip and the pD2 value was 7.61+/-0.89. [MePhe7]-NKB induced small, inconsistent contractions and, therefore, a pD2 value could not be calculated. 4 In experiments performed in the presence of phosphoramidon (1 microM), SR 48968 (3 nM - 0.1 microM) caused parallel and rightward shifts in the log concentration-response curves of NKA. The calculated pKB value was 9.16+/-0.08 and the slope of the Schild regression was 1.28+/-0.24. SR 48968 (0.1 microM) also antagonized responses to SP with an apparent pKB value of 7.63+/-0.13. SR 48968 (0.1 microM) inhibited contractions elicited by NKB (1 nM - 3 microM) and [Nle10]-NKA(4-10) (0.1 nM - 3 microM) but had no effect on the response evoked by [Sar9Met(O2)11]-SP (0.1 microM). 5 SR 140333 (0.1 microM) inhibited responses to SP with an apparent pKB value of 7.19+/-0.22. This compound did not significantly affect responses to NKA, [Nle10]-NKA(4-10) and NKB, but suppressed [Sar9Met(O2)11]-SP (0.1 microM)-induced contraction. SR 142801 (0.1 microM) had no effect on responses to natural tachykinins or their analogues. 6 Total RNA was extracted from some of the uteri used in functional studies. RT-PCR assays revealed single bands corresponding to the expected product sizes encoding cDNA for tachykinin NK1 (587 base pairs) and NK2 receptors (491 base pairs) (n=6 different animals). A very low abundance transcript corresponding to the 325 base pairs product expected for the tachykinin NK3 receptor was detected. 7 The present data show that functionally active tachykinin NK1 and NK2 receptors are expressed in the oestrogen-primed rat uterus. The NK2 receptor type seems to be the most important one involved in the contractile responses elicited by tachykinins. NK3 receptors are present in trace amounts and seem not to be involved in tachykinin-induced contractions.
Assuntos
Estrogênios/farmacologia , Receptores de Taquicininas/fisiologia , Útero/ultraestrutura , Animais , Cálcio/farmacologia , DNA Complementar/genética , DNA Complementar/metabolismo , Feminino , Cinética , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores de Taquicininas/efeitos dos fármacos , Taquicininas/agonistas , Taquicininas/antagonistas & inibidores , Taquicininas/farmacologia , Transcrição Gênica , Útero/efeitos dos fármacos , Útero/fisiologiaRESUMO
D-002 is a natural mixture of high molecular weight alcohols isolated and purified from beeswax, which contains triacontanol among its main components. This study was undertaken to investigate the anti-inflammatory effects of D-002 administered by the oral route in two animal models commonly used in the pharmacological screening of anti-inflammatory drugs. D-002 administered orally to rats (100 and 200 mg/kg) produced a mild but significant reduction of exudate volume in carrageenan-induced pleuritic inflammation that was accompanied by a marked and significant decrease of leukotriene B4 (LTB4) levels in the exudate. D-002 (25, 50 and 200 mg/kg) also significantly diminished the granuloma weight in the cotton pellet granuloma in rats. In both cases, D-002 was less effective than indomethacin, which was used as an established anti-inflammatory reference drug. On the other hand, D-002 administered from 25-1000 mg/kg did not induce erosions or gastromucosal lesions in rats, which differs from results usually obtained with non steroidal anti-inflammatory drugs. These results indicate that D-002 is a mild anti-inflammatory agent without any ulcerogenic effect associated. The results suggest that these effects are probably not mediated through an inhibition of cyclooxygenase, but a reduction in LTB4 levels induced by D-002 could explain these results.
Assuntos
Anti-Inflamatórios/farmacologia , Álcoois Graxos/farmacologia , Ceras/química , Administração Oral , Animais , Anti-Inflamatórios/uso terapêutico , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Carragenina/farmacologia , Álcoois Graxos/uso terapêutico , Mucosa Gástrica/efeitos dos fármacos , Gossypium/metabolismo , Granuloma/induzido quimicamente , Granuloma/tratamento farmacológico , Indometacina/farmacologia , Indometacina/uso terapêutico , Inflamação/tratamento farmacológico , Pleurisia/induzido quimicamente , Pleurisia/tratamento farmacológico , Ratos , Ratos Sprague-DawleyRESUMO
The expression of the tachykinin NK3 receptor and its regulation by ovarian steroids were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) in uteri from ovariectomized rats. A single transcript corresponding to the 325-bp product expected for the tachykinin NK3 receptor was detected in uteri from olive oil-treated (control) ovariectomized rats. The level of tachykinin NK3 receptor mRNA in progesterone-treated animals was similar to that observed in uteri from control ones. Tachykinin NK3 receptor mRNA levels were significantly smaller in uteri from oestrogen-treated ovariectomized rats, with approximately a 32-fold decrease. These findings suggest that oestrogen, but not progesterone, regulates the expression of tachykinin NK3 receptors in the rat uterus.
Assuntos
Estrogênios/farmacologia , Progesterona/farmacologia , Receptores da Neurocinina-3/efeitos dos fármacos , Útero/efeitos dos fármacos , Animais , DNA Complementar/metabolismo , Eletroforese em Gel de Ágar , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Ovariectomia , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores da Neurocinina-3/genética , Útero/metabolismoRESUMO
We investigated the effect of Mn2+ on the mechanical responses evoked by high K+ (60 mM) or low Na+ (25 mM) solutions, oxytocin and neurokinin A in the oestrogen-primed rat uterus. In a Ca2+-free, Mn2+ (0.54 mM)-containing solution, high K+ or low Na+ solutions produced contractions of smaller amplitude than those observed in a normal Ca2+ (0.54 mM) solution, which were abolished by nifedipine (1 microM). Oxytocin (1 microM) and neurokinin A (1 microM, in the presence of phosphoramidon 1 microM) evoked nifedipine-insensitive contractile responses similar to (oxytocin) or smaller (neurokinin A) in amplitude than those observed in Ca2+ (0.54 mM)-containing solution. In strips loaded with Ca2+ (2.16 mM) for 10 min and then exposed to a Ca2+- and Mn2+-free, EGTA (3 mM)-containing medium for 4 min, both oxytocin and neurokinin A induced transient contraction followed by a small sustained response. The transient component of the response was abolished by cyclopiazonic acid (10 microM). When preparations were loaded with Mn2+ (2.16 mM) for 10 min, only the small, tonic contraction was observed. In Ca2+-containing solution, Mn2+ (0.01-10 mM) inhibited in a concentration-dependent manner the rhythmic contractions developed either spontaneously or by electrical stimulation as well as high K+- and neurokinin A-induced contractions. Mn2+ also abolished the rhythmic, but not the tonic component of the response to oxytocin, and the preparation remained maximally contracted. These data suggest that in the oestrogen-primed rat uterus, Mn2+ acts as an antagonist of Ca2+ influx through L-type voltage-operated Ca2+ channels. In addition, Mn2+ enters the cell mainly through nifedipine-insensitive receptor-operated channels and, to a lesser degree, through L-type Ca2+ channels to produce contraction by directly activating the contractile machinery.
Assuntos
Manganês/farmacologia , Neurocinina A/farmacologia , Ocitocina/farmacologia , Potássio/farmacologia , Sódio/farmacologia , Contração Uterina/efeitos dos fármacos , Animais , Cálcio/farmacologia , Avaliação Pré-Clínica de Medicamentos , Estimulação Elétrica , Estrogênios/farmacologia , Feminino , Técnicas In Vitro , Fosfatos de Inositol/biossíntese , Ratos , Ratos WistarRESUMO
In the present study we examine the mechanism by which thaligrisine, a bisbenzyltetrahydroisoquinoline alkaloid, inhibits the contractile response of vascular smooth muscle. The work includes functional studies on rat isolated aorta and tail artery precontracted with noradrenaline or KCl. In other experiments rat aorta was precontracted by caffeine in the presence or absence of extracellular Ca2+. In order to assess whether thaligrisine interacts directly with calcium channel binding sites or with alpha-adrenoceptors we examined the effect of the alkaloid on [3H]-(+)-cis diltiazem, [3H]-nitrendipine and [3H]-prazosin binding to cerebral cortical membranes. The functional studies showed that the alkaloid inhibited in a concentration-dependent manner the contractile response induced by depolarization in rat aorta (IC50 = 8.9+/-2.9 microM, n=5) and in tail artery (IC50 = 3.04+/-0.3 microM, n=6) or noradrenaline induced contraction in rat aorta (IC50 = 23.0+/-0.39 microM, n=9) and in tail artery (IC50 = 3.8+/-0.9 microM, n=7). In rat aorta, thaligrisine concentration-dependently inhibited noradrenaline-induced contraction in Ca2+-free solution (IC50 = 13.3 microM, n=18). The alkaloid also relaxed the spontaneous contractile response elicited by extracellular calcium after depletion of noradrenaline-sensitive intracellular stores (IC50 = 7.7 microM, n=4). The radioligand receptor-binding study showed that thaligrisine has higher affinity for [3H]-prazosin than for [3H]-(+)-cis-diltiazem binding sites, with Ki values of 0.048+/-0.007 microM and 1.5+/-1.1 microM respectively. [3H]-nitrendipine binding was not affected by thaligrisine. The present work provides evidence that thaligrisine shows higher affinity for [3H]-prazosin binding site than [3H]-(+)-cis-diltiazem binding sites, in contrast with tetrandrine and isotetrandrine that present similar affinity for both receptors. In functional studies thaligrisine, acted as an alpha1-adrenoceptor antagonist and as a Ca2+ channel blocker, relaxing noradrenaline or KCl-induced contractions in vascular smooth muscle. This compound specifically inhibits the refilling of internal Ca2+-stores sensitive to noradrenaline, by blocking Ca2+-entry through voltage-dependent Ca2+-channels.
Assuntos
Alcaloides/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Agonistas alfa-Adrenérgicos/metabolismo , Agonistas alfa-Adrenérgicos/farmacologia , Antagonistas Adrenérgicos alfa/metabolismo , Antagonistas Adrenérgicos alfa/farmacologia , Alcaloides/metabolismo , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/metabolismo , Aorta Torácica/fisiologia , Artérias/efeitos dos fármacos , Artérias/metabolismo , Artérias/fisiologia , Sítios de Ligação , Cafeína/farmacologia , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Diltiazem/metabolismo , Diltiazem/farmacologia , Feminino , Técnicas In Vitro , Membranas/efeitos dos fármacos , Membranas/metabolismo , Relaxamento Muscular/fisiologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiologia , Nitrendipino/metabolismo , Nitrendipino/farmacologia , Norepinefrina/farmacologia , Cloreto de Potássio/farmacologia , Prazosina/metabolismo , Prazosina/farmacologia , Ratos , Ratos Wistar , Receptores Adrenérgicos alfa/metabolismo , Cauda/irrigação sanguínea , Árvores/química , Trítio , Vasoconstritores/metabolismo , Vasoconstritores/farmacologiaRESUMO
Policosanol is a mixture of higher aliphatic primary alcohols isolated from sugar cane (Saccharum officinarum L.) and octacosanol represents its main component. This study was conducted to examine the effects of policosanol on myocardial necrosis induced by subcutaneous injection of isoprenaline in rats. A significant reduction (P < 0.01) of infarct size, polymorphonuclear cells and mast cells was observed in animals treated with policosanol at 5 or 25 mg kg-1, while animals receiving only acetysalicylic acid pretreatment showed a significant decrease in the infarct area (P < 0.05). No significant differences in polymorphonuclear and mast cells were obtained when compared with positive control data. It is concluded that policosanol delays the evolution of infarction, showing a protective effect on the myocardial necrosis induced by isoprenaline in this experimental model.
Assuntos
Álcoois Graxos/uso terapêutico , Coração/efeitos dos fármacos , Isoproterenol/toxicidade , Miocárdio/patologia , Inibidores da Agregação Plaquetária/uso terapêutico , Administração Oral , Animais , Aspirina/farmacologia , Glicosaminoglicanos/metabolismo , Isoproterenol/antagonistas & inibidores , Masculino , Mastócitos/efeitos dos fármacos , Necrose , Neutrófilos/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Ratos WistarRESUMO
Policosanol is a mixture of higher aliphatic alcohols isolated from sugar cane wax, showing cholesterol-lowering effects and preventing the development of lipofundin-induced lesions in New Zealand rabbits. This study was conducted to determine whether policosanol orally administered to rats also protects against the development of lipofundin-induced atherosclerotic lesions. Fifty four male Wistar rats were randomly distributed amongst a negative control group, a positive control group intravenously injected with lipofundin for eight days, and four experimental groups also injected with lipofundin, but orally receiving policosanol at 0.5, 2.5, 5 and 25 mg kg-1, respectively. Policosanol treatment was orally administered once-a-day for eight days, while control groups similarly received equivalent amounts of vehicle. A significant reduction of the atherosclerotic lesions in the treated animals was observed. It is concluded that policosanol has a protective effect on lipofundin-induced aortic lesions in Wistar rats.
Assuntos
Anticolesterolemiantes/farmacologia , Arteriosclerose/prevenção & controle , Álcoois Graxos/farmacologia , Fosfolipídeos/farmacologia , Sorbitol/farmacologia , Animais , Aorta/patologia , Arteriosclerose/patologia , Combinação de Medicamentos , Masculino , Ratos , Ratos WistarRESUMO
D-002 is an anti-ulcerogenic product, isolated from beeswax, which consists of a well-defined mixture of higher primary aliphatic alcohols. It is highly effective against ethanol-induced ulcers. This study was designed to determine if D-002 shows cytoprotective properties on gastric mucosa in ethanol-induced ulcers. The involvement of endogenous prostaglandins in the protective effect of D-002 was also investigated. When a subulcerogenic dose of indomethacin (10 mg kg-1) was injected simultaneously with oral administration of ethanol, oral pre-treatment with D-002 (5-100 mg kg-1) partially inhibited the gastric protection. D-002 (5 and 25 mg kg-1) administered to normal rats significantly increased the soluble mucus content and also prevented its reduction in rats with ethanol-induced ulcers. In addition, D-002 administered at 5 and 25 mg kg-1 prevented the increase of vascular permeability induced by ethanol (60%) and reduced the concentration of thromboxane B2 (TXB2) in gastric mucosa of rats with ethanol-induced ulcers. These results support the hypothesis that the anti-ulcerogenic properties of D-002 could be related to a cytoprotective mechanism.
Assuntos
Antiulcerosos/uso terapêutico , Abelhas/química , Álcoois Graxos/uso terapêutico , Úlcera/prevenção & controle , Animais , Permeabilidade Capilar/efeitos dos fármacos , Etanol , Álcoois Graxos/isolamento & purificação , Feminino , Mucosa Gástrica/irrigação sanguínea , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Muco/metabolismo , Prostaglandinas/metabolismo , Ratos , Ratos Sprague-Dawley , Tromboxano B2/metabolismo , Úlcera/induzido quimicamente , Ceras/químicaRESUMO
The stability studies of tablets containing 10 mg of policosanol, a new cholesterol lowering drug, were conducted to predict an expiration date and to search the appearance of putative degradation products. All quality specification parameters such as colour, moisture content, hardness, disintegration, policosanol content and microbiological limits of the tablets were done. The effect of drastic treatments such as acid and basic hydrolysis, oxidative and photolytic degradation as well as thermolysis on such parameters was studied. In addition; studies under drastic conditions of storage (40 degrees C and 75% R.H.) and under ambient conditions of storage for climatic zones II and IV were performed. These studies demonstrate that these tablets are a stable pharmaceutical formulation, without significant changes on their quality criteria at the stressed conditions studied. The chromatographic profile of the samples after 9 months of thermal degradation shows chromatographic peaks that corresponds to the octacosanoyl, triacontanoyl and hexacosanoyl esters of palmitate and stearate, being the only degradation products observed on these studies.
Assuntos
Álcoois Graxos/administração & dosagem , Álcoois Graxos/análise , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/análise , Estabilidade de Medicamentos , Excipientes , Dureza , Temperatura Alta , Hidrólise , Espectrometria de Massas , Oxirredução , Fotólise , ComprimidosRESUMO
The stability studies of tablets containing 5 mg of policosanol, a new cholesterol lowering drug, were conducted to predict an expiration date and to search the appearance of putative degradation products. All quality parameters such as colour, moisture content, hardness, disintegration, policosanol content and microbiological limits of the tablets were assessed. The effect of extreme treatments such as acid and basic hydrolysis, oxidative and photolytic degradation as well as thermal degradation, on the policosanol content was studied. In addition, studies under extreme conditions of storage [(40 +/- 2) degree C and (75 +/- 5)% R.H.] as well as 37, 45, 55 and 60 degrees C combined with 50, 75 and 92% R.H.) and under ambient conditions of storage for climatic zones II and IV were performed. These studies demonstrate that these tablets are a stable pharmaceutical formulation, without significant changes in their quality criteria at the stressed conditions used, so that policosanol content remains unchanged during the entire studies. The chromatographic profile of the samples after 9 months of thermal degradation shows chromatographic peaks that corresponds to the palmitate and stearate esters of octacosanoyl, triacontanoyl and hexacosanoyl, being the only degradation products observed on these studies.
Assuntos
Anticolesterolemiantes/análise , Álcoois Graxos/análise , Cor , Contaminação de Medicamentos , Estabilidade de Medicamentos , Dureza , Solubilidade , ComprimidosRESUMO
The contractile effect of okadaic acid (OA), a highly selective inhibitor of protein serine/threonine phosphatases, was analyzed in the rat uterus during the estrous cycle and during the course of pregnancy. Contractile effects were related to circulating levels of estrogen and progesterone and to mRNA levels of myosin light chain kinase (MLCK) and of myosin light chain protein phosphatase catalytic (PP1-delta) and larger regulatory subunit (MYPT). Both in nonpregnant and pregnant uteri, OA (20 microM) induced a transient contraction, which after plateauing, slowly decreased. In the nonpregnant uterus, the amplitude of this contraction varied at different stages of the estrous cycle, being higher at proestrus and lower at diestrus. In the pregnant uterus, the contraction to OA increased significantly during the course of pregnancy, reaching a maximum in day 21 pregnant rats, and declined after delivery. Whatever the day of pregnancy, the amplitude of the contraction to OA was not significantly modified when obtained in Ca(2+)-free solution. The magnitude of the OA-induced contraction in spontaneously cycling and pregnant rats was positively correlated to the ratio of estrogen/progesterone serum levels. Reverse transcription-polymerase chain reaction assays on myometrial tissue demonstrated that mRNA expression of PP1-delta and MYPT was higher at early (day 3) than at late (day 21) pregnancy. MLCK mRNA levels were similar in day 3 and day 21 pregnant rats. These data suggest that changes in the expression and activity of myosin phosphatase may contribute to modulating the level of uterine contractile force during the estrous cycle, pregnancy, and labor.
Assuntos
Estradiol/fisiologia , Ácido Okadáico/farmacologia , Progesterona/fisiologia , Contração Uterina/efeitos dos fármacos , Útero/efeitos dos fármacos , Animais , Inibidores Enzimáticos/farmacologia , Estradiol/sangue , Feminino , Quinase de Cadeia Leve de Miosina/biossíntese , Quinase de Cadeia Leve de Miosina/genética , Fosfatase de Miosina-de-Cadeia-Leve , Fosfoproteínas Fosfatases/biossíntese , Fosfoproteínas Fosfatases/genética , Gravidez , Progesterona/sangue , RNA Mensageiro/biossíntese , RNA Mensageiro/efeitos dos fármacos , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Útero/fisiologiaRESUMO
In the mammalian female reproductive tract, tachykinin neuropeptides, such as substance P (SP), are localized to a population of sensory fibers and their precise physiological role is still unknown. The aim of the present study was to characterize the population of tachykinin receptors in the pregnant rat uterus and to assess their regulation during the course of pregnancy and after delivery. The expression of the tachykinin NK(1) receptor (NK(1)R), the tachykinin NK(2) receptor (NK(2)R), and the tachykinin NK(3) receptor (NK(3)R) in uteri from rats at different stages of pregnancy and on Day 1 postpartum was investigated by using a semiquantitative reverse transcription-polymerase chain reaction. The contractile effect of tachykinin receptor agonists acting selectively on the NK(1)R, the NK(2)R, or the NK(3)R was investigated by conventional organ bath techniques. Serum levels of estrogen and progesterone were measured by RIA. Our data show that the expression and function of NK(1)R and NK(3)R varied along the course of pregnancy and at postpartum. Uterine NK(2)R mRNA levels remain stable during the course of pregnancy and at Day 1 postpartum; and the contractions elicited by activating selectively the NK(2) receptor in the presence of the neutral endopeptidase inhibitor phosphoramidon (1 microM) were similar in early, mid, or late pregnancy. These results show that the expression and function of tachykinin receptors within the uterus vary with reproductive state and length of gestation, supporting a role for tachykinins in pregnancy and/or parturition in the rat.
Assuntos
Expressão Gênica , Receptores de Taquicininas/genética , Útero/química , Animais , Estradiol/sangue , Feminino , Glicopeptídeos/farmacologia , Piperidinas/farmacologia , Gravidez , Progesterona/sangue , Quinuclidinas/farmacologia , Ratos , Ratos Wistar , Receptores da Neurocinina-1/genética , Receptores da Neurocinina-2/genética , Receptores da Neurocinina-3/genética , Receptores de Taquicininas/agonistas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Contração Uterina/efeitos dos fármacos , Útero/fisiologiaRESUMO
En el proceso de diagnóstico de los pacientes los errores y retrasos pueden comprometer la seguridad del paciente. Se expresa el diseño e implantación de un sistema de mejora del proceso diagnóstico desde el laboratorio clínico. Se desarrolló un sistema basado en intervenciones para completar estudios analíticos con un algoritmo de exploración secuencial y aportar información útil para la interpretación de resultados en la práctica clínica.Se registraron 23.973 intervenciones, que suponían el 8% de los pacientes estudiados. La exploración de la función Hepato-Biliar y metabolismo lipídico fueron las intervenciones más frecuentes realizadas. En conclusión los laboratorios clínicos pueden adoptar una actitud proactiva en el diagnóstico de los pacientes, que supone un valor añadido útil, con previsible impacto favorable en la efectividad y eficiencia clínica en la atención del paciente (AU)
No disponible
Assuntos
Humanos , Melhoria de Qualidade/organização & administração , Laboratórios Hospitalares/normas , Técnicas de Laboratório Clínico/normas , Ensaio de Proficiência LaboratorialAssuntos
Cistectomia , Disfunção Erétil/tratamento farmacológico , Papaverina/uso terapêutico , Fentolamina/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Papaverina/administração & dosagem , Ereção Peniana , Fentolamina/administração & dosagem , Autoadministração , Fatores de TempoAssuntos
Síndrome da Imunodeficiência Adquirida/complicações , Anfotericina B/uso terapêutico , Antiprotozoários/farmacologia , Leishmaniose Visceral/tratamento farmacológico , Meglumina/farmacologia , Compostos Organometálicos/farmacologia , Adulto , Anfotericina B/efeitos adversos , Antimônio/farmacologia , Resistência a Medicamentos , Humanos , Masculino , Antimoniato de Meglumina , Pentamidina/uso terapêutico , Abuso de Substâncias por Via Intravenosa/complicaçõesRESUMO
La hospitalización domiciliaria (HD) constituye un sistema de atención sociosanitaria alternativa a la hospitalización tradicional que resulta coste-efectiva. El objetivo del presente trabajo es estudiar la utilización de medicamentos en la unidad de HD, tomando como unidad de medida el número de DDD/100 estancias, así como identificar los tipos de pacientes más frecuentemente atendidos y establecer una relación con el consumo de medicamentos y el coste de los mismos. Para ello se ha realizado un estudio prospectivo de los pacientes ingresados en esta unidad durante el período enero-marzo de 1999. Se utilizó con este fin una hoja de recogida de datos que fue completada a partir de las epicrisis de los pacientes a su ingreso en HD, y cuando fue necesario, a partir de la historia clínica. También se obtuvieron los consumos de medicamentos por paciente a partir del módulo de dosis unitarias Farmasyst-APD y los datos de consumo global y coste a partir del módulo de gestión. En total se analizaron 130 ingresos (correspondientes a 125 pacientes con una media de edad de setenta y tres años). La media de diagnósticos por ingreso fue de 2,4 y el número de estancias por ingreso de dieciocho días. El coste por ingreso fue de 11.542 pesetas y el coste por estancia de 641 pesetas. Las patologías de mayor frecuencia de presentación fueron neoplasias, enfermedades respiratorias (infecciones, síndromes obstructivos, insuficiencia respiratoria) y enfermedades cardiovascu¡ares (insuficiencia cardiaca y cardiorrespiratoria, accidentes cardiovasculares, etc.). El número de DDD/100 estancias por grupo terapéutico puede desglosarse de la siguiente forma, por orden de mayor a menor: grupo respiratorio: 33,4; grupo digestivo: 24,5; grupo terapia hormonal (corticoides): 21,1; grupo cardiovascular: 14,2; grupo sistema nervioso (incluyendo analgésicos): 10,0; grupo antiinfecciosos: 7,5; grupo sangre y órganos hematopoyéticos: 4,0, y grupo dietéticos: 0,55. (AU)