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1.
Sci Rep ; 13(1): 11292, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37438441

RESUMO

The influence of heat treatment processes on microstructure, tensile and tribological properties of Ti6Al4V alloy was investigated. The specimens were heated for 30 min at 925 °C and then cooled at various rates by water quenching, air cooling, and furnace cooling. After that, the samples were aged for four hours at 600 °C. Three phases make up the microstructure: primary α-phase (αp), secondary α-phase (αs), and retained ß-phase (ßr). Cooling in the air and water followed by aging (AC + Aging and WQ + Aging) resulted, αs-phase precipitating inside ßr-phase. The highest hardness of 35 HRC was recorded for WQ + Aging specimen due to existence of a high amount of ßr-phase and precipitation of αs-phase. On the other hand, the lowest hardness of 26 HRC was obtained for the FC specimen. AC specimen achieved the highest elongation value of 14%. However, WQ + Aging specimen exhibited the highest ultimate tensile strength of 1028 MPa. For WQ + Aging and AC + Aging specimens, the ideal balance of strength and elongation was discovered. The wear resistance of solution-treated specimens was significantly improved by the aging process and 125% improvement could be achieved in WQ compared to WQ + Aging specimens.

2.
Sci Rep ; 13(1): 11249, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37438461

RESUMO

Protective oxide layers on Ti-6Al-3Mo-2Nb-2Sn-2Zr-1.5Cr (TC21) alloy with equiaxed microstructure considerably influence micro-hardness and hot corrosion resistance. The present work's thermal oxidation of TC21 alloy was performed at 600, 700, and 800 °C for 5, 20, and 50 h durations. Hot corrosion methods in NaCl and NaCl + Na2SO4 salt media were applied to raw (unoxidized) and oxidized samples at 600 and 800 °C for 50 h. Hot corrosion was conducted at 600 °C for 5 cycles with 10-h steps. The best oxide layer thickness was observed at 800 °C, which increased with increased oxidation time and temperature. The surface hardness of the oxide layer at 800 °C was 900 ± 60 HV0.05 owing to the formation of TiO2 and Al2O3 phases. Raw material hardness was 342 ± 20 HV0.05, increasing threefold due to thermal oxidation. In the case of NaCl, weight loss dominated all samples except at 800 °C for 5 h. In the case of NaCl + Na2SO4, weight gain occurred at 600 and 800 °C for 5 h. Weight loss occurred for the raw samples and those processed at 800 °C for 20 and 50 h, where the oxide layer flaked off. Surface hardness increased upon hot corrosion testing because of the formation of brittle phases, such as TiO2 and Na4Ti5O12. Samples that oxidized at 800 °C for 5 h had the highest hardness and corrosion resistance.

3.
Sci Rep ; 13(1): 8878, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37264044

RESUMO

This study aims at investigating worn surface topography and mathematical modeling of annealed Ti-6Al-3Mo-2Sn-2Zr-2Nb-1.5Cr alloy using response surface methodology (RSM). The alloy was subjected to three different regimes in order to study their effect on mechanical properties. First regime was applying cold deformation by compression until 15% drop in height at room temperature. The second regime was performing solution treated on the deformed samples at 920 °C for 15 min then air-cooled (AC) to ambient temperature. Third regime was applying aging on the deformed and solution treated specimen for 4 hr at 590 °C followed by air-cooling. Three different velocities (1, 1.5, and 2 m/s) were adopted to conduct dry sliding wear according to the experimental design technique (EDT). Gwyddion and Matlab softwares were used to detect worn surface photographs analytically and graphically. Maximum hardness of 425 HV20 was obtained for AC+Aging specimen, while minimum hardness of 353 HV20 was reported for the annealed specimen. Applying aging process after solution treatment enhanced considerably the wear property and this enhancement reached 98% as compared to the annealed condition. The relationship between input factors (hardness & velocity) and responses (Abbott Firestone zones) was demonstrated using analysis of variance (ANOVA). The best models for Abbott Firestone zones (high peaks, exploitation, and voids) produced accurate data that could be estimated for saving time and cost. The results showed that the average surface roughness increases with increasing sliding velocity for all conditions except AC+Aging condition where the average surface roughness decreased with increasing sliding velocity. The results revealed that at low velocity and hardness, the material gives the highest exploitation zone (86%). While at high velocity and hardness, the material gives the lowest exploitation zone (70%). In general, the predicted results of mathematical model showed close agreement with experimental results, creating that models could be utilized to predict Abbott Firestone zones satisfactorily.

4.
Sci Rep ; 13(1): 6929, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37117244

RESUMO

Aluminum closed cell foam blocks are created with a volume of 1 inch3 which consist of aluminum foam parts shielded with part of aluminum tube and in some types reinforced with inner aluminum tubes. Blocks have been made to overcome some existing problems in metallic foam used to protect some applications parts from impacts as a sacrificial part. Metallic foam has three main categories sandwich panels, filled tubes and corrugated sheets. Quasi-static compression tests have been applied on 12 blocks with different shapes and compared with pure aluminum foam blocks as a reference. Results display the enhancement of mechanical properties of blocks like yield strength (SY), crushing strength (Sc) and densification strength (Sd), compression at strain 70%, as well as absorbed energy (area of compression under the curve). The highest value for yield strength (5.87 MPa) was registered for Finger phalanxes cube block (FP-0.1 Sq.). While the highest value for densification strength (21.7 MPa) was registered for spine cylinder block (SV8-0.17 C25). The registered results for samples apparent the highest value for energy dissipation density (Edd) is 40.52 J/in3 (91% enhancement) and crushing strength (8.61 MPa) was registered for Finger phalanx cylinder block (FP-0.17 C25). The lowest value for Edd is 14.16 J/in3 (less than pure aluminum foam block value by 33%), SY = 0.42 MPa, Sc = 3.21 MPa, and Sd = 4.46 MPa, registered for thin wall Ear canal cylinder block (EC8-0.075 C26.5). Best mechanical properties had been achieved for Finger phalanx cylinder block (FP-0.17 C25) and spine cylinder block (SV8-0.17 C25).

5.
Sci Rep ; 13(1): 4624, 2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36944750

RESUMO

This study investigated the effect of heat treatment processes on the dry sliding wear resistance of the TC21 Ti-alloy at several levels of normal load and sliding speed. Response Surface Methodology (RSM) has been used as a design of the experiment procedure. OM and FESEM besides XRD analysis were used for results justification. Highest hardness of 49 HRC was recorded for WQ + Aging specimens due to the plenty of α″ which decomposed to αs and the more αs, while the lowest hardness of 36 HRC was reported for WQ specimens. The results revealed that specimens subjected to water quenching and aging (WQ + Aging) under extreme load and speed conditions (50 N and 3 m/s), possessed the poorest wear resistance although they had the highest hardness. While those left in the annealed condition revealed the highest wear resistance although they had much lower hardness when compared to other conditions. A mathematical polynomial model for wear resistance expressed in wear rate was developed, validated then used to get the optimum parameters.

6.
Sci Rep ; 12(1): 19265, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357445

RESUMO

In the current study on TC21 Ti-alloy (6.5Al-3Mo-1.9Nb-2.2Sn-2.2Zr-1.5Cr), the thermal oxidation formed oxide layers that considerably influenced mechanical properties (hardness and wear). TC21 specimens were oxidized at 600, 700, 800, and 900 °C for 5, 20, and 50 h. NaCl-induced hot corrosion testing was carried out on raw (un-oxidized) and oxidized specimens at 600 and 800 °C for 50 h. The cyclic testing was performed at 600 °C for durations of 5, 10, 20, 30, 40, and 50 h. The average thickness of the layer grew with increasing oxidation time and temperature. A thin oxide layer (average 0.16 µm) was generated by oxidation at a temperature of 600 °C for a duration of 5 h, and at 800 °C, a large oxide layer of 10.8 µm thickness was formed. The most significant surface hardness of 1000 ± 150 HV0.05 was produced for the layer oxidized at 900 °C. On the other hand, the lowest hardness of 360 ± 150 HV0.05 was recorded for the raw materials. Best wear resistance had been achieved for specimens oxidized at 800 °C. During NaCl hot corrosion test, the weight loss of the raw specimen was 6.4 mg/cm2 due to the flaking off of the corrosion product. However, for specimens oxidized at 600 °C for 50 h, weight loss after corrosion testing was 0.54 mg/cm2, less than that of the specimen before corrosion. Oxidized specimens at 800 °C exhibited the best mechanical characteristics and corrosion resistance.

7.
Sci Rep ; 12(1): 14472, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36008539

RESUMO

The effects of applied pressure and running velocity on wear behavior as well as Abbott Firestone zones of low carbon steel (0.16C) were evaluated using response surface methodology (RSM). At room temperature, three different pressures (0.5, 1.5, and 2.5 MPa) and three different velocities (1.5, 2.25, and 3 m/s) were used to conduct dry sliding wear trials utilizing the pin-on-disc method according to the experimental design technique (EDT). The experiments were created using central composite design (CCD) as a starting point. The relationship between input factors (pressure and velocity) and responses (wear rate and Abbott Firestone zones) of 0.16C steel was demonstrated using analysis of variance (ANOVA). The best models for wear rate as well as Abbott Firestone zones produced accurate data that could be estimated, saving time and cost. The results revealed that pressure had the greatest impact on the alloy's dry sliding wear behavior of the two variables studied. In general, the predicted result shows close agreement with experimental results and hence created models could be utilized for the prediction of wear behavior and Abbott Firestone zones satisfactorily.

9.
Micromachines (Basel) ; 12(7)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202536

RESUMO

The TC21 alloy (Ti-6Al-3Mo-1.9Nb-2.2Sn-2.2Zr-1.5Cr) is considered a new titanium alloy that replaced the commercial Ti-6Al-4V alloy in aerospace applications due to its higher operating temperatures. Recently, direct energy deposition was usually applied to enhance the hardness, tribological properties, and corrosion resistance for many alloys. Consequently, this study was performed by utilizing direct energy deposition (DED) on TC21 (α/ß) titanium alloy to improve their mechanical properties by depositing a mixture powder of stellite-6 (Co-based alloy) and tungsten carbides particles (WC). Different WC percentages were applied to the surfaces of TC21 using a 4 kW continuous-wave fiber-coupled diode laser at a constant powder feeding rate. This study aimed to obtain a uniform distribution of hard surfaces containing undissolved WC particles that were dispersed in a Co-based alloy matrix to enhance the wear resistance of such alloys. Scanning electron microscopy, energy dispersive X-ray analysis (EDAX), and X-ray diffractometry (XRD) were used to characterize the deposited layers. New constituents and intermetallic compounds were found in the deposited layers. The microhardness was measured for all deposited layers and wear resistance was evaluated at room temperature using a dry sliding ball during a disk abrasion test. The results showed that the microstructure of the deposited layer consisted of a hypereutectic structure and undissolved tungsten carbide dispersed in the matrix of the Co-based alloy that depended on the WC weight fraction. The microhardness values increased with increasing WC weight fraction in the deposited powder by more than threefold as compared with the as-cast samples. A notable enhancement of wear resistance of the deposited layers was thus achieved.

10.
Infez Med ; 28(4): 545-550, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33257629

RESUMO

In late December 2019, the COVID-19 pandemic started to spread from Hubei province in China. Currently there are many affected countries worldwide, including Saudi Arabia. This study aimed to assess the use of social media as a source for COVID-19 awareness in Saudi Arabia. An online survey was conducted between 9 and 13 May 2020 and a total of 3,204 subjects participated in the survey. We used snowball sampling techniques through an online structured questionnaire. The data were cleaned, coded and analysed using the Statistical Package for the Social Sciences SPSS version 25.0. A chi-square test was used to find the associations between variables. Of all participants, 75.4% had a high level of awareness of the COVID-19 pandemic. Saudi participants above 18 years old and medical practitioners showed a high level of awareness. All participants from all regions of Saudi Arabia showed a high level of awareness except for those from the northern region. The most common source of information was the official government social media, and 44.1% reported the use of Twitter. Our findings show that social media have a positive impact on the circulation of information about the COVID-19 pandemic in Saudi Arabia.


Assuntos
COVID-19/epidemiologia , Disseminação de Informação/métodos , Pandemias , SARS-CoV-2 , Mídias Sociais/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Conscientização , Distribuição de Qui-Quadrado , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Médicos/estatística & dados numéricos , Arábia Saudita/epidemiologia , Estudantes/estatística & dados numéricos , Desemprego/estatística & dados numéricos , Adulto Jovem
11.
J Neonatal Perinatal Med ; 9(1): 73-82, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27002258

RESUMO

OBJECTIVE: Visfatin is a hormone discovered in fat cells and is directly related to diabetes. We aimed to investigate the relationship between intrauterine growth pattern and serum visfatin concentrations in full-term infants at birth and at 6 months of life. METHODS: Cord blood visfatin concentrations were assessed in 90 full-term neonates enrolled into; Group I: 30 appropriate for gestational age (AGA) neonates to healthy mothers, Group II: 30 intra-uterine growth restricted (IUGR) neonates, 19 were born to mothers with pre-eclampsia, Group III: 30 large for gestational age (LGA) neonates, 16 were infants of diabetic mothers (IDMs). Neonates were followed up at six months of age for visfatin concentrations. RESULTS: Cord blood visfatin concentrations were increased in IUGR compared to AGA group (p = 0.002). Cord blood visfatin concentrations were increased in LGA compared to AGA and IUGR groups (P <  0.001, P <  0.001). Cord blood visfatin concentrations were positively correlated to birth weight in AGA, LGA groups (r = 0.39, p = 0.045, r = 0.449, p = 0.013 respectively). Visfatin concentrations in neonates born to mothers with pre-eclampsia and IDMs were higher than in those born to mothers without pre-eclampsia and to non-diabetic mothers (p = 0.040, p = 0.002 respectively). At six months, serum visfatin concentrations decreased compared to cord blood visfatin concentrations in IUGR and LGA groups (p <  0.001). Levels in LGA were still higher than IUGR (p = 0.004). Serum visfatin concentrations were positively correlated to cord visfatin in IUGR neonates (r = 0.497, p = 0.005). CONCLUSION: Cord blood visfatin concentrations were increased in LGA and IUGR neonates. At six months, serum visfatin concentrations decreased compared to cord blood visfatin concentrations in LGA and IUGR groups, still higher in the former than the latter.


Assuntos
Citocinas/sangue , Retardo do Crescimento Fetal/sangue , Nicotinamida Fosforribosiltransferase/sangue , Pré-Eclâmpsia/sangue , Gravidez em Diabéticas/sangue , Adulto , Biomarcadores/sangue , Peso ao Nascer , Estudos de Casos e Controles , Egito , Feminino , Sangue Fetal , Retardo do Crescimento Fetal/fisiopatologia , Seguimentos , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Masculino , Pré-Eclâmpsia/fisiopatologia , Gravidez , Gravidez em Diabéticas/fisiopatologia
12.
Infection ; 40(3): 279-84, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22189516

RESUMO

PURPOSE: Cryptosporidium species is considered to be an important cause of significant morbidity in immunocompromised individuals. A prospective case-control study of sporadic diarrhea due to Cryptosporidium infection was conducted on children with acute lymphoblastic leukemia (ALL). METHODS: Forty children with ALL on maintenance chemotherapy according to the Berlin-Frankfurt-Munster (BFM-90) protocol and 45 sex- and age-matched controls were studied. The ALL group included 25 patients with acute diarrhea and 15 without diarrhea, and the control group included 30 children with acute diarrhea and 15 without. Collected stool specimens were examined using modified Ziehl-Neelsen (MZN) and modified trichrome stains. Serum Cryptosporidium Parvum immunoglobulin G (IgG) antibodies were detected by enzyme-linked immunosorbent assay. RESULTS: Cryptosporidium oocysts, pathogenic Gram-negative organisms, Giardia lamblia, and Entamoeba histolytica were identified in the stool samples (fecal specimens) of six (24%), eight (32%), four (16%), and two (8%), respectively, of the 25 patients with ALL and actute diarrhea and in one (3%), two (6.5%), six (20%), and five (16.5%), respectively, of the 30 control patients with diarrhea. Serum IgG antibodies were positive in four of the six ALL patients and in one of the control group patients with Cryptosporidium diarrhea who tested positive for oocysts in the stool. Diarrhea duration and severity were greater in ALL patients with stool-positive Cryptosporidium oocysts than in those with non-Cryptosporidium-positive diarrhea (p < 0.000). CONCLUSIONS: Cryptosporidium infection should be considered in children with ALL presenting with prolonged or severe watery diarrhea during chemotherapy, especially those treated with methotrexate and 6-mercaptopurine. Since Cryptosporidium is not routinely tested for in stool examination, a MZN stain is recommended.


Assuntos
Criptosporidiose/parasitologia , Cryptosporidium parvum/isolamento & purificação , Gastroenterite/parasitologia , Mercaptopurina/uso terapêutico , Metotrexato/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Criptosporidiose/imunologia , Diarreia/imunologia , Diarreia/parasitologia , Egito , Entamoeba histolytica/isolamento & purificação , Fezes/microbiologia , Fezes/parasitologia , Feminino , Gastroenterite/imunologia , Giardia lamblia/isolamento & purificação , Bactérias Gram-Negativas/isolamento & purificação , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Lactente , Quimioterapia de Manutenção/efeitos adversos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/parasitologia , Estudos Prospectivos
13.
Curr Med Res Opin ; 23(12): 3177-87, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17991308

RESUMO

OBJECTIVE: To compare systemic delivery of ergotamine tartrate (ET) via a breath-synchronized, plume-control inhaler (BSPCI) (Tempo ET) with a sublingual ergot preparation and a commercial inhaler. METHODS: Study 1 determined plasma ET concentrations in seven healthy subjects after administration of ET by a 2 mg tablet (Lingraine) and a BSPCI delivering 258 microg of ET. Study 2 determined plasma ET concentrations in 16 healthy subjects after administration via an ET metered dose inhaler (ME) (Medihaler) delivering 2052 microg of ET and a BSPCI delivering 129 microg of ET. Gamma scintigraphy with (99m)Tc validation was used to quantify lung deposition. RESULTS: For both studies, ET C(max) was higher with the BSPCI (study 1: sublingual ET 134 pg/mL at 37 min; BSPCI 3743 pg/mL at 3 min; study 2: metered-dose inhaler 1109 pg/mL at 4 min; BSPCI 1210 pg/mL at 2.5 min). Mean dose normalized AUC was several-fold higher with the BSPCI compared with sublingual ET and ME dosing. Lung deposition of ET with the BSPCI was 33.5, 8.9, 11.4, and 13.2% for whole, central, intermediate, and peripheral lung, respectively, with a 1.5 peripheral : central ratio. CONCLUSION: Based on these open-label studies, the BSPCI allows rapid delivery of potentially therapeutic plasma concentrations of ET at approximately 1/15th the dose of comparators.


Assuntos
Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/farmacocinética , Ergotamina/administração & dosagem , Ergotamina/farmacocinética , Inaladores Dosimetrados , Transtornos de Enxaqueca/tratamento farmacológico , Administração por Inalação , Adolescente , Adulto , Aerossóis , Idoso , Analgésicos não Narcóticos/sangue , Ergotamina/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Comprimidos , Distribuição Tecidual
14.
Cephalalgia ; 26(2): 150-7, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16426269

RESUMO

Headache is a frequent accompaniment of acute ischaemic stroke. The predisposing factors and underlying mechanisms are currently incompletely defined. We analysed prospectively collected data relevant to headache occurring at ischaemic stroke onset in consecutive patients included in the Henry Ford Hospital Stroke Data Bank. Patients with headache (HA+) and without headache (HA-) were compared for demographic factors, medical history, medications, examination findings, laboratory findings, and stroke localization and subtype. Group comparisons for categorical data were performed with chi(2) test, and for continuous variables with two-sample t-tests. Stepwise logistic regression analysis, including all variables with P<0.25, was used to define the independent predictors of onset headache. Three hundred and seventy-five patients had complete headache and clinical datasets and were included in the analysis (HA+, N=118; HA-, N=257). Multivariate analysis revealed that the independent predictors of HA+ were: infarct in the distribution of the posterior circulation [P=0.0076, odds ratio (OR) 2.15, 95% confidence interval (CI) 1.23, 3.77], absence of history of hypertension (P=0.0106, OR 0.48, 95% CI 0.27, 0.84), and treatment with warfarin at the time of the index stroke (P=0.0135, OR 4.89, 95% CI 1.39, 17.21). The occurrence of headache at onset of ischaemic stroke is determined by posterior circulation distribution of the ischaemic event, absence of history of hypertension and treatment with warfarin at the time of the index stroke. These results suggest that preserved elasticity and maintenance of the intracranial vasculature in a relaxed state, in combination with coagulation system derangements, and activation of dense perivascular afferent nerves, play a role in the pathogenesis of onset headache.


Assuntos
Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiologia , Cefaleia/diagnóstico , Cefaleia/epidemiologia , Medição de Risco/métodos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Doença Aguda , Idoso , Comorbidade , Bases de Dados Factuais , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
16.
Cephalalgia ; 24(7): 596-602, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15196302

RESUMO

Glutamatergic hyperactivity is implicated migraine pathogenesis. Also, LY293558, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate (KA) receptor antagonist, is effective in preclinical models of migraine. We therefore tested LY293558 in acute migraine. We conducted a randomized, triple-blind, parallel-group, double-dummy, multicentre trial of 1.2 mg/kg intravenous (IV) LY293558, 6 mg subcutaneous (SC) sumatriptan, or placebo in the treatment of acute migraine. The primary efficacy variable was the headache response rate, i.e. headache score improvement from moderate/severe at baseline to mild/none at 2 h. Of 45 enrolled patients, 44 patients (20M:24F; mean age +/- SD = 40 +/- 9 years) completed the study. Response rates were 69% for LY293558 (P = 0.017 vs. placebo), 86% for sumatriptan (P < 0.01 vs. placebo) and 25% for placebo. LY293558 and sumatriptan were superior to placebo (P < 0.01 for all comparisons) on all other measures of improvement in pain and migraine associated symptoms. Fifteen percent of patients who took LY293558 reported adverse events (AEs) (n = 2; one mild, one severe). Fifty-three percent of patients who took sumatriptan (n = 8; seven mild, one moderate) and 31% of those who received placebo reported AEs (n = 5; four mild, one severe). The efficacy and safety results of LY293558 in this small migraine proof of concept trial, together with supportive preclinical data, provide evidence for a potential role of nonvasoactive AMPA/KA antagonists in treating migraine. Larger trials are needed to further test the hypothesis.


Assuntos
Isoquinolinas/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Receptores de AMPA/antagonistas & inibidores , Receptores de Ácido Caínico/antagonistas & inibidores , Tetrazóis/uso terapêutico , Doença Aguda , Adulto , Análise de Variância , Distribuição de Qui-Quadrado , Feminino , Humanos , Isoquinolinas/farmacologia , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/metabolismo , Receptores de AMPA/metabolismo , Receptores de Ácido Caínico/metabolismo , Tetrazóis/farmacologia
17.
Cephalalgia ; 23(8): 776-85, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14510923

RESUMO

Serotonin-1F receptor (5-HT1F) agonists may relieve acute migraine without vasoconstriction. We conducted a review of preclinical and clinical data that assessed the potential link between migraine and 5-HT1F activation. (i) A high correlation exists between the potency of various 5-HT1 receptor agonists in the guinea pig dural plasma protein extravasation assay and their 5-HT1F receptor binding affinity. (ii) 5-HT1F receptors are on the trigeminal system, and may participate in blocking migraine pain transmission through the trigeminal ganglion and nucleus caudalis. (iii) 5-HT1F receptors are located on glutamate-containing neurones and their activation might inhibit glutamate release; glutamate excess may play a role in migraine. (iv) Selective 5-HT1F receptor agonists (LY334370; LY344864) are effective in preclinical migraine models and are non-vasoconstrictive. (v) LY334370 is effective in acute migraine, and does not cause any symptoms/signs of coronary vasoconstriction. Preclinical experiments and clinical observations argue for a role of selective 5-HT1F agonists in migraine.


Assuntos
Transtornos de Enxaqueca/tratamento farmacológico , Receptores de Serotonina/metabolismo , Agonistas do Receptor de Serotonina/uso terapêutico , Doença Aguda , Animais , Ensaios Clínicos como Assunto/estatística & dados numéricos , Humanos , Transtornos de Enxaqueca/metabolismo , Receptor 5-HT1F de Serotonina
18.
Expert Opin Investig Drugs ; 12(4): 545-59, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12665411

RESUMO

The pharmacotherapy for pain is dominated by conventional analgesics such as the opioids and the non-steroidal anti-inflammatory drugs. Recent advances in the understanding of the mechanisms of pain in general and chronic pain in particular, opened the field of analgesic therapy to newer pharmacological targets, which are aimed at improved efficacy and enhanced tolerability over conventional antipain treatments. Many novel targets are still in preclinical development, but some have made it into human trials and have shown promise. Newer anticonvulsants, new generation cyclooxygenase inhibitors, better tolerated glutamate modulators and balanced serotonin/noradrenaline re-uptake inhibitors are some targets that have shown promise in the clinic. These and other compounds that are in advanced phases of development for chronic pain are reviewed in this paper. It is hoped that the decade of pain control and research will lead us to an arsenal of effective and safe analgesics that will conquer the problem of chronic pain.


Assuntos
Analgésicos/uso terapêutico , Dor/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Canabinoides/uso terapêutico , Doença Crônica , Humanos , Dor/metabolismo , Bloqueadores dos Canais de Sódio/uso terapêutico
20.
Neurology ; 60(4): 630-3, 2003 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-12601104

RESUMO

BACKGROUND: Current evidence-based acute treatments of cluster headache are limited to oxygen inhalation and subcutaneous sumatriptan. Intranasal sumatriptan is a new formulation with better tolerability than the subcutaneous route. Two open-label studies suggested efficacy of intranasal sumatriptan in cluster headache. METHODS: In a double-blind placebo-controlled randomized trial, patients with episodic or chronic cluster headache whose attacks lasted at least 45 minutes each treated one attack with 20 mg sumatriptan nasal spray and another one, at least 24 hours later, with matching placebo. They scored their headache on a five-point scale (very severe, severe, moderate, mild, or none) at 5, 10, 15, 20, and 30 minutes. The primary outcome measure was headache response (a decrease in pain from very severe, severe, or moderate to mild or none) at 30 minutes. Secondary outcome measures included pain-free rates, relief of associated symptoms, and rates of adverse events. Multilevel multivariate analysis was used for statistical analysis. RESULTS: Five study centers enrolled 118 patients in whom 154 attacks were treated: 77 with sumatriptan and 77 with placebo. The responder rates at 30 minutes were 57% for sumatriptan and 26% for placebo (p = 0.002). Pain-free rates at 30 minutes were 47% for sumatriptan and 18% for placebo (p = 0.003). Sumatriptan was also superior to placebo considering initial response, meaningful relief, and relief of associated symptoms. There were no serious adverse events. CONCLUSION: Sumatriptan nasal spray is effective and well tolerated in the acute treatment of cluster headache attacks of at least 45 minutes' duration.


Assuntos
Cefaleia Histamínica/tratamento farmacológico , Agonistas do Receptor de Serotonina/uso terapêutico , Sumatriptana/uso terapêutico , Administração Intranasal , Adulto , Estudos de Coortes , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Agonistas do Receptor de Serotonina/administração & dosagem , Agonistas do Receptor de Serotonina/efeitos adversos , Sumatriptana/administração & dosagem , Sumatriptana/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
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