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2.
Comput Methods Programs Biomed ; 130: 46-53, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27208520

ABSTRACT

BACKGROUND AND OBJECTIVE: In oral and maxillofacial surgery, conventional radiographic cephalometry is one of the standard auxiliary tools for diagnosis and surgical planning. While contemporary computer-assisted cephalometric systems and methodologies support cephalometric analysis, they tend neither to be practical nor intuitive for practitioners. This is particularly the case for 3D methods since the associated landmarking process is difficult and time consuming. In addition to this, there are no 3D cephalometry norms or standards defined; therefore new landmark selection methods are required which will help facilitate their establishment. This paper presents and evaluates a novel haptic-enabled landmarking approach to overcome some of the difficulties and disadvantages of the current landmarking processes used in 2D and 3D cephalometry. METHOD: In order to evaluate this new system's feasibility and performance, 21 dental surgeons (comprising 7 Novices, 7 Semi-experts and 7 Experts) performed a range of case studies using a haptic-enabled 2D, 2½D and 3D digital cephalometric analyses. RESULTS: The results compared the 2D, 2½D and 3D cephalometric values, errors and standard deviations for each case study and associated group of participants and revealed that 3D cephalometry significantly reduced landmarking errors and variability compared to 2D methods. CONCLUSIONS: Through enhancing the process by providing a sense of touch, the haptic-enabled 3D digital cephalometric approach was found to be feasible and more intuitive than its counterparts as well effective at reducing errors, the variability of the measurements taken and associated task completion times.


Subject(s)
Cephalometry/methods , Computer Simulation , User-Computer Interface , Adult , Humans , Middle Aged , Young Adult
4.
Pharm. care Esp ; 15(4): 147-156, jun.-jul. 2013. tab
Article in Spanish | IBECS | ID: ibc-115112

ABSTRACT

El tratamiento del trastorno por déficit de atención e hiperactividad (TDAH) incluye intervenciones farmacológicas, psicosociales y educativas, y en él se aconseja un diseño personalizado teniendo en cuenta las características del paciente, el tipo de trastorno y la comorbilidad que lo acompaña. Los fármacos de primera línea son el psicoestimulante metilfenidato (MTF) y atomoxetina (ATX), un simpaticomimético de acción central no estimulante. Ambos reducen las manifestaciones clínicas de inquietud, inatención e impulsividad, mejorando la calidad de las relaciones sociales y el rendimiento académico. Metilfenidato bloquea el transportador presináptico de dopamina (DA) y noradrenalina (NA), aumentando la concentración de estos neurotransmisores en el espacio presináptico neuronal. Se presenta en formas de liberación inmediata (LI) (Rubifen® y Medicebran® en preparados de acción prolongada con tecnología OROS® [osmotic controlled-release oral delivery system], Concerta® y Metilfenidato Sandoz®) y en pellets (Medikinet®), que permiten seleccionar adecuadamente la dosis y la pauta posológica. Las formas de LI pueden inducir efecto rebote al provocar un pico plasmático elevado que decae en poco tiempo. Atomoxetina (Strattera®) es un inhibidor muy selectivo y potente del transportador presináptico de NA; aumenta los niveles de NA y DA en la corteza prefrontal, pero no en las regiones corticales relacionadas con el desarrollo de tics o riesgo de abusos de sustancias. Puede ser la alternativa a MTF cuando éste pierde eficacia o está contraindicado. La efectividad de ambos fármacos debe considerarse a partir de las 2-4 semanas. Sus reacciones adversas son numerosas y con frecuencia causan malestar, lo que dificulta la adherencia. Por ello es necesario el seguimiento de estos pacientes, y el farmacéutico puede ejercer un papel destacado para mejorar el cumplimiento y los efectos de la farmacoterapia(AU)


Treatment of attention deficit hyperactivity disorder (ADHD) includes pharmacological, psychosocial and educational interventions. A custom designed treatment taking into account patient characteristics, type of disorder and comorbidity must be advisable. First election drugs are the psychostimulant methylphenidate (MTF) and the sympathomimetic not stimulant atomoxetine (ATX). These drugs reduce the clinical manifestations of restlessness, inattention and impulsivity, improving the quality of social relationships and academic performance. MTF blocks the presynaptic dopamine (DA) and norepinephrine (NA) transporters increasing the concentration of these neurotransmitters in the presynaptic neuron. Both of them are available in the pharmaceutical forms of immediate release (IR) (Rubifen ® and Medicebran®, prolonged acting preparations with OROS® [osmotic controlled-release oral delivery system] technology, Concerta® and Metilfenidato Sandoz®) and pellets (Medikinet®), allowing a proper selection of dosage pattern. IR pharmaceutical forms can induce rebounding effect by causing high plasma peak that decays quickly. ATX is a highly selective and a potent inhibitor of presynaptic NA transporter, increasing levels of NA and DA in the prefrontal cortex, but not in cortical regions related to the development of tics or risk of substance abuse. It can be an alternative to MTF when this loses effectiveness or is contraindicated. The effectiveness of both drugs must be considered after 2 to 4 weeks of treatment. Their side effects are numerous and often cause discomfort making difficult adherence. Therefore it is necessary to monitor these patients playing pharmacist a leading role in improving the performance and the effects of pharmacotherapy(AU)


Subject(s)
Humans , Male , Female , Attention Deficit Disorder with Hyperactivity/epidemiology , Attention Deficit Disorder with Hyperactivity/prevention & control , Methylphenidate/therapeutic use , Norepinephrine/therapeutic use , Attention Deficit Disorder with Hyperactivity/drug therapy , Attention Deficit Disorder with Hyperactivity/metabolism , Comorbidity , Dopamine/therapeutic use , Combined Modality Therapy/methods , Combined Modality Therapy
5.
Eur J Intern Med ; 24(5): 420-4, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23428531

ABSTRACT

BACKGROUND: The original Medication Appropriateness Index was validated for elderly and polymedicated patients, both in hospital and outpatient contexts. However, no studies have applied this questionnaire in patients with multiple chronic conditions. The objective of this study is to assess the reliability of a modified Medication Appropriateness Index questionnaire in a population of patients with multiple chronic conditions. METHODS: We selected patients with multiple chronic conditions who were included in an integrated care project conducted at the Hospital Universitario Virgen del Rocío. To determine inter-observer reliability, each professional (internist or hospital pharmacy specialist) applied the questionnaire under the same conditions and with the same resources. To determine intra-observer reliability, each physician applied the tool at baseline and two months later. We measured inter- and intra-observer reliability using the kappa coefficient. The proportion of overall agreement was also determined. RESULTS: We obtained a weak overall kappa (k=0.38) for inter-observer reliability and moderate (k=0.52) and very good (k=0.84) values for intra-observer reliability of the internist and specialist in hospital pharmacy, respectively. The proportion of overall agreement is very high in all three situations: 96%, 98%, and 99%, respectively. CONCLUSIONS: Despite its limitations, the Medication Appropriateness Index questionnaire modified by our group can be used, as a reliable method, to assess the appropriateness of pharmacotherapy in patients with multiple chronic conditions.


Subject(s)
Chronic Disease/drug therapy , Chronic Disease/epidemiology , Drug Therapy, Combination/standards , Surveys and Questionnaires/standards , Aged , Aged, 80 and over , Comorbidity , Drug Therapy, Combination/statistics & numerical data , Female , Humans , Male , Observer Variation , Reproducibility of Results
6.
Mini Rev Med Chem ; 11(4): 298-344, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21428901

ABSTRACT

Epidemiological studies have revealed that a diet rich in plant-derived foods has a protective effect on human health. Identifying bioactive dietary constituents is an active area of scientific investigation that may lead to new drug discovery. Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g. tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries and grapes) and in plants or botanical products commonly used in traditional medicine (e.g. Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Some epidemiological studies have found a positive association between the consumption of foods containing kaempferol and a reduced risk of developing several disorders such as cancer and cardiovascular diseases. Numerous preclinical studies have shown that kaempferol and some glycosides of kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, anti-osteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic and antiallergic activities. In this article, the distribution of kaempferol in the plant kingdom and its pharmacological properties are reviewed. The pharmacokinetics (e.g. oral bioavailability, metabolism, plasma levels) and safety of kaempferol are also analyzed. This information may help understand the health benefits of kaempferol-containing plants and may contribute to develop this flavonoid as a possible agent for the prevention and treatment of some diseases.


Subject(s)
Kaempferols/chemistry , Cardiovascular Diseases/prevention & control , Dietary Supplements , Humans , Kaempferols/pharmacokinetics , Kaempferols/therapeutic use , Medicine, Traditional , Neoplasms/prevention & control , Plants/chemistry
7.
Br J Nutr ; 86(3): 349-57, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11570987

ABSTRACT

The effects of two monounsaturated fatty acid (MUFA)-rich diets, containing virgin olive oil (OO) and high-oleic-acid sunflower oil (HOSO), on development of vascular response from isolated thoracic rat aorta and lipid composition and fatty acid composition were studied and compared with samples from rats fed on a control diet. Dietary MUFA oils were fed for 6 weeks to spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats from 4 weeks of age. The maximum contraction of aortic ring preparations in response to phenylephrine (10(-6) m) was significantly decreased in SHR rats fed with OO (0.81 (sem 0.05) v. 1.18 (sem 0.09) g, and treatment with HOSO did not alter the phenylephrine-induced contractions. The relaxant responses to acetylcholine (10(-5) m) were significantly enhanced (30.03 (sem 0.70) v. 18.47 (sem 0.28) %, in the rings from SHR rats treated with OO, and were more pronounced than in WKY rats In the same way, OO attenuated the dose-response curves induced by phenylephrine (10(-8)-10(-5) m) from SHR rats, accompanied with a slower contraction. These results suggest that only the chronic feeding of OO diet was able to attenuate the vascular response of rat aorta. In addition, an increase in phospholipid content (186.7 (sd 3.2) v. 159.1 (sd 11.3) g/kg, and changes in the fatty acid composition of aorta (mainly a decrease in arachidonic acid) could contribute to improving endothelial function. Therefore, the effects can not be attributed exclusively to the content of MUFA (mainly oleic acid). Other components of OO, such as polyphenols, not present in HOSO, may help to explain the vascular protective effect of OO consumption.


Subject(s)
Hypertension/metabolism , Oleic Acid/administration & dosage , Vascular Resistance/drug effects , Acetylcholine/pharmacology , Animals , Aorta/chemistry , Case-Control Studies , Dose-Response Relationship, Drug , Fatty Acids/analysis , In Vitro Techniques , Lipids/analysis , Male , Oleic Acid/analysis , Olive Oil , Phenylephrine/pharmacology , Phospholipids/chemistry , Plant Oils/chemistry , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Sunflower Oil , Vasoconstrictor Agents/pharmacology , Vasodilator Agents/pharmacology
8.
J Ethnopharmacol ; 76(3): 279-84, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11448550

ABSTRACT

Cecropia obtusifolia (Cecropiaceae) is a species from tropical America and its leaves are used in traditional medicine for the treatment of diabetes and as an anti-inflammatory agent. In the present study, the analgesic, anti-inflammatory and central nervous system depressant effects of the aqueous extract from the leaves of C. obtusifolia were investigated in different experimental models, with the purpose of validating its ethnomedical uses. The results obtained with the extract from the leaves of C. obtusifolia reflect a low toxicity, a substantial central depressor effect and analgesic activity and significant motor incoordination and muscle relaxant activity. Concerning the analgesic activity, using the hot plate test, the extract did not produce any effect, however it showed a significant effect on the pain induced by chemical stimuli (acetic and formalin test); this suggests the peripheral analgesic effect of the extract. The extract also showed a topical and systemic anti-inflammatory effect. Thus this work could justify the popular use of C. obtusifolia in rheumatic and kidney inflammation pathologies and reveals that this plant is an interesting species.


Subject(s)
Analgesics/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Central Nervous System Depressants/pharmacology , Phytotherapy , Plant Extracts/pharmacology , Rosales , Analgesics/isolation & purification , Animals , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Behavior, Animal/drug effects , Central Nervous System/drug effects , Edema/chemically induced , Edema/prevention & control , Lethal Dose 50 , Male , Mice , Models, Animal , Motor Activity/drug effects , Muscle Relaxation/drug effects , Pain/chemically induced , Pain/prevention & control , Plant Extracts/therapeutic use , Plants, Medicinal
9.
Eur J Pharmacol ; 415(2-3): 217-24, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11275002

ABSTRACT

This report is focused on the study of simvastatin-induced relaxation of rat aorta through its effects on vascular smooth muscle and Ca(2+) signalling. The presence of endothelium affected only the simvastatin-induced relaxation of aortic rings precontracted with noradrenaline, but not by depolarization with KCl 80 mM. Blockade of Ca(2+) entry through voltage-operated Ca(2+) channels (VOCCs) by diltiazem abolished the endothelium-dependent and direct relaxation, whereas Ca(2+)-ATPase inhibition by cyclopiazonic acid (3 x 10(-5) M) only affected the endothelium-dependent relaxation. In KCl-depolarised arteries concentration-response curves for CaCl(2) were shifted to the right in the presence of simvastatin (3 x 10(-6) and 3 x 10(-5) M) or diltiazem (10(-6) and 10(-7) M). The transient contraction caused by noradrenaline in Ca(2+)-free medium, which is mainly due to intracellular Ca(2+) release, was inhibited by simvastatin (3 x 10(-5) M) or cyclopiazonic acid (3 x 10(-5) M) and the contraction induced by CaCl(2) (2 x 10(-3) M) added after noradrenaline was inhibited by diltiazem and simvastatin. All the reported effects of simvastatin were inhibited by the product of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, mevalonate (10(-3) M). These findings demonstrate that the vascular effects of simvastatin may involve both Ca(2+) release from intracellular stores, which could promote activation of endothelial factors, and blockade of extracellular Ca(2+) entry, which promote relaxations independent of the presence of endothelium. This action on Ca(2+) could be related to the inhibition of isoprenoid synthesis, which subsequently affects the function of G-proteins involved in communication among intracellular Ca(2+) pools and capacitative Ca(2+) entry.


Subject(s)
Calcium Signaling/drug effects , Endothelium, Vascular/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Muscle, Smooth, Vascular/drug effects , Simvastatin/pharmacology , Vasodilation/drug effects , Animals , Calcium Signaling/physiology , Diltiazem/pharmacology , Endothelium, Vascular/physiology , Indoles/pharmacology , Male , Mevalonic Acid/pharmacology , Muscle, Smooth, Vascular/physiology , Rats , Rats, Wistar , Vasodilation/physiology , Vasodilator Agents/pharmacology
10.
Z Naturforsch C J Biosci ; 55(1-2): 121-4, 2000.
Article in English | MEDLINE | ID: mdl-10739111

ABSTRACT

Simvastatin is an inhibitor of HMG-CoA reductase used in the treatment of hypercholesterolemia. In the present study simvastatin-induced contraction was observed in rat aortic thoracic rings, this effect increased when the endothelium was removed and when NO synthase was blocked by L-NOARG (3 x 10(-5) M). The contractile effect of simvastatin on intact aortic rings diminished when cyclo-oxygenase was inhibited with indomethacin (10(-5) M). Also in the presence of endothelium, pretreatment with mevalonate (1 mM), the product of HMG-CoA reductase activity, significantly inhibited the contraction. In other experiments carried out on endothelium-removed preparations and in medium containing the calcium antagonist, diltiazem (10(-5) and 10(-6) M), the contraction dose-response curves were significantly reduced and the same happened in the presence of the inhibitor of sarcoplasmic reticulum Ca-2+-ATPase, cyclopiazonic acid (CPA) (3 x 10(-6) M). The results suggest that simvastatin might increase intracellular calcium concentration. This effect could lead to an activation of NO synthase and cyclooxygenase pathways in endothelial cells and to contraction in vascular smooth muscle cells. This rise in Ca2+ concentration could be due to an inhibition of isoprenoid synthesis prevented by mevalonate.


Subject(s)
Aorta, Thoracic/physiology , Endothelium, Vascular/physiology , Muscle Contraction/physiology , Muscle, Smooth, Vascular/physiology , Simvastatin/pharmacology , Animals , Aorta, Thoracic/drug effects , Diltiazem/pharmacology , In Vitro Techniques , Indoles/pharmacology , Indomethacin/pharmacology , Male , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , Nitroarginine/pharmacology , Rats , Rats, Wistar , Vasodilator Agents/pharmacology
11.
J Hypertens ; 17(6): 769-76, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10459874

ABSTRACT

OBJECTIVE: To investigate the effects of chronic treatment with simvastatin (SV) on endothelium-dependent relaxation and ouabain-induced contractions in aortic rings from spontaneously hypertensive rats (SHR), comparing with normotensive Wistar-Kyoto rats (WKY). METHODS: After a 12-week period of administration of 1 or 2 mg/kg SV to SHR and WKY, systolic blood pressure (SBP) and vascular reactivity in endothelium-intact aortic rings were assessed. RESULTS: Relaxation in response to acetylcholine (ACh) in WKY remained unaltered, but in SHR treated with 1 mg/kg SV, enhanced ACh-induced relaxation (P<0.05 versus untreated SHR) reached values observed in untreated WKY. The 2 mg/kg treatment also improved ACh relaxation (P<0.01 and P<0.05 versus untreated SHR and WKY respectively). Inhibiting cyclo-oxygenase (COX) with indomethacin (INDO) improved ACh relaxation in SHR (P<0.05) but not in WKY, independent of treatment with SV. Inhibition of nitric oxide synthase (NOS) with N(G)-nitro-L-arginine (L-NOARG) abolished ACh relaxations in all cases (P<0.001). The result was unaltered when combining INDO plus L-NOARG. SV treatment also decreased ouabain-induced contractions in endothelium-intact aortic rings from SHR, diminishing the percentage effect of contraction from 64.56+/-2.95 (untreated SHR) to 26.98+/-7.06 and 38.10+/-8.21 (1 and 2 mg/kg treated SHR respectively). Response to ouabain in WKY was not significantly affected by SV treatment CONCLUSIONS: Chronic treatment of SHR with SV improves endothelium-dependent ACh relaxation of the aortic rings, probably by an NO-involving mechanism more than by inhibiting contractile COX-derived factors. An improvement in endothelial modulation of ouabain-induced contractions was also observed after treatment with SV in SHR, which might be due to an inhibition of a calcium-sodium exchanger.


Subject(s)
Endothelium, Vascular/physiopathology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypertension/drug therapy , Simvastatin/therapeutic use , Vasodilation/drug effects , Acetylcholine/pharmacology , Animals , Aorta, Thoracic/drug effects , Aorta, Thoracic/enzymology , Aorta, Thoracic/physiopathology , Blood Pressure/drug effects , Cardiotonic Agents/pharmacology , Endothelium, Vascular/drug effects , Endothelium, Vascular/enzymology , Enzyme Inhibitors/pharmacology , Follow-Up Studies , Hypertension/enzymology , Hypertension/physiopathology , Male , Nitric Oxide Synthase/antagonists & inhibitors , Nitroarginine/pharmacology , Ouabain/pharmacology , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Vasodilator Agents/pharmacology
12.
Ginecol Obstet Mex ; 66: 330-4, 1998 Aug.
Article in Spanish | MEDLINE | ID: mdl-9745194

ABSTRACT

Bethesda system is useful in the citologic diagnosis of premalign diseases of cervix. It was determined the correlation between citologic report using Bethesda system and combined colposcopic index (CCI) or Reid, to diagnose premalign diseases of cervix by histologic diagnostic of punch biopsy by colposcopy. A total of 118 patients come to the colposcopy clinic having smear anormal citology to cervical intraepithelial neoplasia (CIN), only o associated to HPV. It was taken to all of them a new cervical smear, colposcopy and punch biopsy. We analized the findings for citology with Bethesda system and colpospic with CCI of Reid, using histologic diagnosis of punch biopsy by colposcopy. Diagnosis correlation between Bethesda system and the punch biopsy by colposcopy was 98.5% for 82 patients with low grade squamous intraepithelial lesions with a concordance of 100% for HPV and 97% for CNI I (p < 0.05). In the other hand 92% from 36 patients classified as high grade squamous intraepithelial lesions with a concordance of 84% to CIN II and 100% to CIN III (p < .05) Sensibility of 93%, especifidad and positive predictive value of 96% and negative predictive value of 98%. We conclude correlation between citologic report with Bethesda system and the Combined Colposcopic Index of Reid which are effective to diagnose premalign disease of cervix.


Subject(s)
Biopsy/methods , Uterine Cervical Diseases/diagnosis , Uterine Cervical Neoplasms/diagnosis , Biopsy/instrumentation , Cervix Uteri/pathology , Colposcopy , Diagnosis, Differential , Female , Humans , Uterine Cervical Diseases/pathology , Uterine Cervical Neoplasms/pathology
13.
Gen Pharmacol ; 30(3): 331-6, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9510082

ABSTRACT

1. Lovastatin (1, 1.5, and 2 mg/kg) decreased systolic (SBP) and diastolic blood pressure (DBP) in spontaneously hypertensive rats (SHRs) and did not modify the basal values of blood pressure in normotensive rats. 2. Lovastatin decreased heart rate in a dose-dependent manner, and significant effects were observed in SHRs 180 min after lovastatin administration. 3. Lovastatin did not act as a diuretic drug at any of the doses used. 4. Lovastatin (10[-6] M-3 x 10[-4] M) depresses contractions evoked by KCl (80 mM) in isolated thoracic aorta from SHRs and WRs and had almost no relaxant effects on NA-induced (10[-5] M) contractions. 5. It is concluded that the main antihypertensive mechanism of lovastatin is due to the relaxation of rat aorta by inhibiting Ca2+ influx through voltage-sensitive calcium channels.


Subject(s)
Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Heart Rate/drug effects , Lovastatin/pharmacology , Muscle, Smooth, Vascular/drug effects , Animals , Aorta , Depression, Chemical , Male , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/physiology , Nifedipine/pharmacology , Rats , Rats, Inbred SHR , Rats, Wistar
14.
Z Naturforsch C J Biosci ; 52(9-10): 687-93, 1997.
Article in English | MEDLINE | ID: mdl-9373998

ABSTRACT

Zolpidem is an imidazopyridine sedative-hypnotic which interacts with central benzodiazepine-receptors. To examine its effects on uterine smooth muscle we have compared with those obtained by diltiazem, papaverine and diazepam on different experimental models. The IC50 values obtained indicate similar behaviour of zolpidem and diazepam. They showed more active against the spontaneous contractions and those induced by KCl (60 mM) or by CaCl2 (0.01-10 mM) in Ca(2+)-free depolarizing medium than against acetylcholine (0.1 mM)-induced contractions. Both of them also showed more effectiveness against the tonic component of the acetylcholine-evoked contraction than against the phasic one. All the drugs tested were less powerful against contractions induced by oxytocin than against those induced by other agonists. This observation let us speculate that the mechanism of action of zolpidem may be related to an action on Ca2+ influx through voltage-dependent Ca2+ channels due to an interaction with low affinity receptor located at the plasmalemma as has been suggested for diazepam.


Subject(s)
Diazepam/pharmacology , Muscle Relaxants, Central/pharmacology , Muscle, Smooth/physiology , Pyridines/pharmacology , Uterine Contraction/drug effects , Uterus/physiology , Acetylcholine/pharmacology , Animals , Calcium Chloride/pharmacology , Diltiazem/pharmacology , Female , Hypnotics and Sedatives/pharmacology , In Vitro Techniques , Muscle Relaxation/drug effects , Muscle, Smooth/drug effects , Oxytocin/pharmacology , Papaverine/pharmacology , Potassium Chloride/pharmacology , Rats , Rats, Wistar , Uterine Contraction/physiology , Uterus/drug effects , Zolpidem
15.
Pharmacol Res ; 35(5): 493-7, 1997 May.
Article in English | MEDLINE | ID: mdl-9299217

ABSTRACT

This study was designed to examine the inhibitory effects exerted by tetrazepam isolated rat duodenum and guinea pig ileum contractive responses and to further clarity the mechanisms involved. Tetrazepam produced concentration-dependent and complete relaxation of muscle contractions induced by KCl (80 mM) in guinea-pig ileum and this relaxant action was not antagonized by pretreatment with hexamethonium (0.1 mM), antagonist for nicotinic receptors, or atropine (1 microM), antagonist for muscarinic receptors, or PK 11195 (1 microM) antagonist for peripheral-type benzodiazepines receptors. Tetrazepam also modified the concentration-response curves of CaCl2 in calcium-free and high K/ depolarizing medium as soon as concentration-response curves of acetylcholine in Tyrode solution. The results suggested that tetrazepam inhibits the contractile responses to guinea-pig ileum and rat duodenum, probably through a reduction of calcium influx by way of calcium channels and these events are not related to high-affinity peripheral benzodiazepine binding sites.


Subject(s)
Anti-Anxiety Agents , Benzodiazepines , Benzodiazepinones/pharmacology , Duodenum/drug effects , Ileum/drug effects , Parasympatholytics/pharmacology , Acetylcholine/antagonists & inhibitors , Acetylcholine/pharmacology , Animals , Calcium Chloride/antagonists & inhibitors , Calcium Chloride/pharmacology , Female , Guinea Pigs , In Vitro Techniques , Male , Muscle Contraction/drug effects , Muscle Relaxation/drug effects , Muscle, Smooth/drug effects , Potassium Chloride/antagonists & inhibitors , Potassium Chloride/pharmacology , Rats , Rats, Wistar
16.
Pharmacol Res ; 36(3): 237-42, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9367669

ABSTRACT

The vasodilating effects of tetrazepam (1,4-benzodiazepine derivative) were studied and compared with those of the K-channel activator, cromakalim and the Ca-channel blocker, diltiazem, in rat aorta smooth muscle and on the spontaneous contractile activity of the rat portal vein. In the aorta, tetrazepam (3 x 10(-7)-10(-4) M) and diltiazem (10(-8)-3 x 10(-6) M) concentration-dependently relaxed aortic rings contracted by 30 mM as well as 80 m KCl. Although cromakalim (10(-8)-3 x 10(-6) M) concentration-dependently relaxed aortic rings contracted by 30 mM KCl, it did not relax those contrated by 80 mm KCl. In the presence of the ATP-sensitive K-channel blocker, glibenclamide (10(-6) and 3 x 10(-6) M), 30 mM KCl concentration-response curves for the relaxant effect of tetrazepam and diltiazem were unaffected but cromakalim caused a progressive shift of these curves upwards. In the portal vein, tetrazepam inhibited spontaneous contractions, decreased amplitude and increased frequency. Similar behaviour was shown with diltiazem (10(-8)-10(-5) M) and in both cases, pre-treatment with glibenclamide (10(-6) M) was ineffective. Although cromakalim (10(-5)-10(-6) M) decreased both amplitude and frequency, this effect was blocked by glibenclamide. These results indicate that the vasodilator action of tetrazepam is not mediated to the opening of ATP-sensitive K-channels, unlike cromakalim. This may be mediated, like those of diltiazem, by the blockade of calcium movements across the cell membrane.


Subject(s)
Anti-Anxiety Agents , Benzodiazepines , Benzodiazepinones/pharmacology , Calcium Channel Blockers/pharmacology , Cromakalim/pharmacology , Diltiazem/pharmacology , Muscle, Smooth, Vascular/drug effects , Potassium Channels/agonists , Vasodilator Agents/pharmacology , Animals , Aorta/drug effects , Aorta/physiology , Female , In Vitro Techniques , Male , Muscle, Smooth, Vascular/physiology , Portal Vein/drug effects , Portal Vein/physiology , Rats , Rats, Wistar
17.
J Pharm Pharmacol ; 48(11): 1169-73, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8961167

ABSTRACT

Tetrazepam is a benzodiazepine derivative clinically used as a muscle relaxant. The aim of the present work was to examine its effect on uterine smooth muscle of the rat in estrus. Tetrazepam required micromolar concentrations to relax contractile responses induced by KCl and acetylcholine in Ca2+ solution, but not oxytocin-induced contraction. In Ca(2+)-free solution, tetrazepam inhibited Ca(2+)-induced contractions in depolarized uterus and vanadate-induced contractions. We suggest that tetrazepam relaxes contractile responses induced by activation of voltage-sensitive calcium channels and receptor-operated calcium channels with little selectivity or that it antagonizes the effect of calcium at subsequent steps, possibly intracellular stores sensitive to vanadate but not sensitive to oxytocin. The inhibition of contraction of rat uterus is not related to high-affinity peripheral benzodiazepine binding sites.


Subject(s)
Anti-Anxiety Agents , Benzodiazepines , Benzodiazepinones/pharmacology , Muscle Relaxants, Central/pharmacology , Muscle, Smooth/drug effects , Uterus/drug effects , Animals , Calcium/metabolism , Calcium Channels/metabolism , Dose-Response Relationship, Drug , Female , Isoquinolines/pharmacology , Muscle Contraction/drug effects , Muscle Relaxation/drug effects , Muscle, Smooth/metabolism , Potassium Chloride/pharmacology , Rats , Rats, Wistar , Uterus/metabolism , Vanadates/pharmacology
18.
J Auton Pharmacol ; 16(2): 105-10, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8842871

ABSTRACT

1. Tetrazepam (TZP) suppressed rat and guinea-pig tracheal tone by 100% and there was no difference in the relaxant effects against tone induced by 120 mM K+, carbachol (0.5 microM) or histamine (100 microM). 2. In trachealis pretreated with propranolol (1 microM), the relaxant response to TZP was unaltered. 3. TZP (10 microM) added to the relaxant effect of isoprenaline in tissues precontracted with carbachol. 4. The relaxant effect of TZP appears to be unrelated to peripheral benzodiazepine receptors (PBRs) because pretreatment with PK 11195 (1 microM) did not modify its effect. 5. Diltiazem (a calcium antagonist) was capable of relaxing the KCl (120 mM) or carbachol (0.5 microM) precontracted trachea, although at a different dose range than that of TZP. 6. The tracheal relaxation by TZP may be due to competition at some point in the chain of events linking carbachol, K+ or histamine to contraction, interacting with one of the transduction pathways, probably Ca2+. This inhibition of contraction is not related to the high-affinity PBRS.


Subject(s)
Anti-Anxiety Agents , Benzodiazepines , Benzodiazepinones/pharmacology , Muscle Relaxants, Central/pharmacology , Muscle, Smooth/drug effects , Trachea/drug effects , Animals , Calcium Channel Blockers/pharmacology , Carbachol/pharmacology , Diltiazem/pharmacology , Female , Guinea Pigs , Histamine/pharmacology , In Vitro Techniques , Isoproterenol/pharmacology , Isoquinolines/pharmacology , Male , Muscle Relaxation/drug effects , Muscle Relaxation/physiology , Muscle, Smooth/physiology , Potassium/pharmacology , Propranolol/pharmacology , Rats , Receptors, GABA-A/drug effects , Receptors, GABA-A/physiology , Trachea/physiology
19.
Pharmacology ; 49(3): 144-50, 1994 Sep.
Article in English | MEDLINE | ID: mdl-7972328

ABSTRACT

This study was designed to determine the gastroprotective properties of naringin on and the involvement of endogenous prostaglandins in mucosal injury produced by absolute ethanol. Oral pretreatment with the highest dose of naringin (400 mg/kg), 60 min before absolute ethanol was the most effective antiulcer treatment. Subcutaneous administration of indomethacin (10 mg/kg) to the animals treated with naringin (400 mg/kg) partially inhibited gastric protection, but the prostaglandin E2 determination did not show any increase in prostanoid levels. The contents of gastric mucus and total proteins were not significantly modified. Naringin-treated rats showed a marked increase in hexosamine levels, but this increase was less in animals pretreated with indomethacin. These results show that naringin has a 'cytoprotective' effect against ethanol injury in the rat, but this property appears to be mediated by non-prostaglandin-dependent mechanisms.


Subject(s)
Anti-Ulcer Agents/pharmacology , Flavanones , Flavonoids/pharmacology , Gastric Mucosa/drug effects , Stomach Ulcer/prevention & control , Animals , Carbenoxolone/pharmacology , Dinoprostone/metabolism , Ethanol/toxicity , Gastric Mucosa/metabolism , Hexosamines/metabolism , Indomethacin/pharmacology , Male , Mucus/metabolism , Rats , Rats, Wistar , Stomach Ulcer/chemically induced
20.
Gen Pharmacol ; 25(3): 575-80, 1994 May.
Article in English | MEDLINE | ID: mdl-7926608

ABSTRACT

1. This study was designed to demonstrate the cytoprotective effect of Rutin against ethanol-induced gastric injury in rats and to determine whether this cytoprotective effect is mediated by endogenous prostaglandins. 100 and 200 mg/kg of Rutin given orally 1 hr before administration of 1 ml of 100% ethanol significantly (p < 0.01) reduced the area of macroscopic lesions induced by ethanol (84.16 +/- 23.01 and 54.75 +/- 16.05 respectively) when compared to distilled water (305.60 +/- 67.20). However, it did not induce changes in the amount and total proteins and hexosamines content of gastric mucus. 2. Pretreatment with indomethacin, 10 mg/kg s.c. 30 min before Rutin administration, slightly but not significantly reduced the cytoprotective effect. 3. The levels of PGE2 present in the mucous material were not significantly modified with administration of Rutin (100 mg/kg). 4. These results show that Rutin has a cytoprotective effect against ethanol injury in the rat, but this property does not appear to be mediated by endogenous prostaglandins.


Subject(s)
Ethanol/antagonists & inhibitors , Gastric Mucosa/drug effects , Gastrointestinal Hemorrhage/prevention & control , Prostaglandins/physiology , Rutin/pharmacology , Stomach Ulcer/prevention & control , Animals , Edema/chemically induced , Edema/prevention & control , Gastric Mucosa/blood supply , Gastrointestinal Hemorrhage/chemically induced , Indomethacin/pharmacology , Male , Rats , Rats, Wistar , Stomach Diseases/chemically induced , Stomach Diseases/prevention & control , Stomach Ulcer/chemically induced
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