RESUMO
BACKGROUND: Orally administered chemical thromboprophylactic agents for total hip replacement (THR) have become popular in recent years. Certain clinical trials suggest that the efficacy and the risk of major bleeding after administration of direct thrombin inhibitor dabigatran etexilate are equivalent to the clinical trial comparator, subcutaneous low-molecular-weight heparin enoxaparin. Our aim was to compare and evaluate the incidence of minor haemorrhagic and soft-tissue adverse effects of enoxaparin and dabigatran. MATERIALS AND METHODS: 122 patients who were treated by elective cemented primary THR were enrolled in our quasi-randomised study. Two groups were formed according to which perioperative thromboprophylactic agent was used: 61 patients in enoxaparin group versus 61 patients in dabigatran group. Thigh volume changes, calculated perioperative blood loss, area of haematoma, wound bleeding, duration of wound discharge and intensity of serous wound discharge on postoperative day 3 and day 7 were recorded. RESULTS: The duration and intensity of serous wound discharge differed significantly between the two groups. Duration of wound discharge after drain removal was 2.2 (±2.7) days in the dabigatran group and 1.2 (±1.9) days in the enoxaparin group (p < 0.05). Significant increase in serous discharge was found in the dabigatran group (p < 0.05) on third and seventh postoperative days compared to the enoxaparin group. CONCLUSION: Both thromboprophylactic agents were found to have appropriate antithrombotic effects after THR. However, dabigatran was associated with an increased incidence of prolonged serous wound discharge, which might cause longer hospitalization and might instigate the use of prolonged antibiotic prophylaxis.
Assuntos
Anticoagulantes/administração & dosagem , Artroplastia de Quadril/métodos , Benzimidazóis/administração & dosagem , Enoxaparina/administração & dosagem , Hemorragia Pós-Operatória/prevenção & controle , beta-Alanina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Artroplastia de Quadril/efeitos adversos , Benzimidazóis/efeitos adversos , Dabigatrana , Enoxaparina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/etiologia , Estudos Prospectivos , beta-Alanina/administração & dosagem , beta-Alanina/efeitos adversosRESUMO
It is well known that a multitude of ligands and receptors are involved in the nociceptive system, and some of them increase, while others inhibit the pain sensation both peripherally and centrally. These substances, including neurotransmitters, neuromodulators, hormones, cytokines etc., may modify the activity of nerves involved in the pain pathways. It is also well known that the organism can express very effective antinociception in different circumstances, and during such situations the levels of various endogenous ligands change. Accordingly, a very exciting field of pain research relates to the roles of endogenous ligands. The peripheral action may possibly be extremely important, because low doses of the endogenous ligands may reduce pain without disphoric side-effects, and without the abused potential typical of centrally acting ligands. This review provides a comprehensive overview of the endogenous ligands that can induce antinociception, discusses their effects on different receptors and focuses on their action at peripheral level. We found 17 different endogenous ligands which produced antinociception after their topical administration. The results suggest an important direction for the development of pain strategies that focus on the local administrations of different endogenous ligands.
Assuntos
Analgésicos Opioides/metabolismo , Metabolismo dos Lipídeos , Neuropeptídeos/metabolismo , Neurotransmissores/metabolismo , Dor/metabolismo , Sistema Nervoso Periférico/metabolismo , Animais , Anexina A1/metabolismo , Citocinas/metabolismo , Endorfinas/metabolismo , Fármacos Atuantes sobre Aminoácidos Excitatórios/metabolismo , Hemoglobinas/metabolismo , Ácido Cinurênico/metabolismo , Ligantes , Melatonina/metabolismo , Camundongos , Oligopeptídeos/metabolismo , Peptídeos Opioides/metabolismo , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Fragmentos de Peptídeos/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Ratos , Somatostatina/metabolismo , beta-Endorfina/metabolismo , NociceptinaRESUMO
BACKGROUND: There are various techniques available to remove a cemented femoral component and distal cement in the case of septic or aseptic loosening, periprosthetic or component fracture. The present study describes the mechanical effects of three techniques: the transfemoral approach (TFA), the distal fenestration technique (DF) and the retrograde stem removal technique (RSR). An experiment on cadaveric femora was performed to establish if there are any differences in the resistance to fracture in and between the various groups. METHODS: Twenty-two paired femora were recovered from human cadavers and were frozen. These were later subdivided into three groups to provide similar specimens in each group (TFA, DF, RSR). The femora were tested using an Instron 8874 biaxial testing system. The torque required to fracture was measured. Intra- and intergroup statistical analysis was performed. RESULTS: In the TFA group, the force required till fracture was significantly less than in controls. (p = 0.018). Similar results were found in the DF group (p = 0.048). There was no difference in the RSR group (p = 1). Intergroup analysis showed the following: Femora in the TFA group required significantly less force to fracture than specimens in the DF group (p = 0.018) or the RSR group (p = 0.0055). Femora in the DF group required significantly less force to fracture than specimens in the RSR (p = 0.037). CONCLUSIONS: The TFA technique decreases the mechanical resistance of human cadaveric femora very significantly against rotational forces. The DF technique in the same setup also significantly decreases the resistance of bone, whilst no significant change is seen with the RSR technique.
Assuntos
Cimentação , Remoção de Dispositivo/métodos , Articulação do Quadril/cirurgia , Prótese de Quadril , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Fenômenos Biomecânicos , Cimentos Ósseos , Cadáver , Humanos , Pessoa de Meia-Idade , Falha de Prótese , Reoperação/métodos , Sensibilidade e EspecificidadeRESUMO
The goal of this study is to determine and compare the ß-endorphin levels in the synovial fluid of patients with different joint disorders (avascular necrosis, AVN; osteoarthritis, OA; and rheumatoid arthritis, RA of the hip or knee). Eighty-seven patients were involved in our study with an average age of 62 years. Thirty-three patients had AVN (18 hips, 15 knees). Twenty-three patients were diagnosed with OA (14 hips, 9 knees), and 31 patients suffered from RA (12 hips, 19 knees). We measured the ß-endorphin levels of the synovial fluids -harvested from surgery-with radioimmunoassay. No significant difference was found in the ß-endorphin levels of the synovial fluid from AVN comparing to OA and RA, however ß-endorphin level was significantly higher in RA group than among patients with OA (p = 0.01). Synovial ß-endorphin level was slightly lower in knee comparing to hip joint p = (0.06). When examining the different joints separately in compliance with diagnoses, we concluded that the synovial ß-endorphin level from AVN was between the values of OA and RA without significant difference, whereas it was significantly higher in the knee of RA, than of OA groups (p = 0.05 knee, p = 0.2 hip). Our results confirmed those experiments which stated that there is a significant increase in synovial ß-endorphin level in patients with inflammatory autoimmune diseases (e.g., RA), comparing to the level measured in degenerative conditions (e.g., OA).
Assuntos
Artrite Reumatoide/metabolismo , Osteoartrite/metabolismo , Osteonecrose/metabolismo , Líquido Sinovial/metabolismo , beta-Endorfina/metabolismo , Idoso , Feminino , Cabeça do Fêmur , Humanos , Articulação do Joelho , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
Diminished pain sensitivity in schizophrenic patients has been reported for more than 50 years, however little is known about the substrate and the basic mechanisms underlying altered pain sensitivity in this disease, therefore, relevant animal models are of decisive importance in the study of psychiatric diseases. The authors report a review consisting of two parts focusing on pain sensitivity changes in patients and in different animal models which proved the eligibility as schizophrenia models and pain sensitivities have also been determined. The second part of this article analyzed the results regarding knock out mice as schizophrenia models. These data proved that several genes have significant role in the pathomechanism of schizophrenia; therefore deficiency in one gene does not produce animals showing all signs of this disease. As regards the pain sensitivity changes, only a few data are available with controversial results. Data originated from complex chronic animal models indicate that they might be more adequate methods for studying the mechanisms of schizophrenia including the pain-sensitivity changes.
Assuntos
Neurotransmissores/metabolismo , Limiar da Dor , Dor/fisiopatologia , Esquizofrenia/fisiopatologia , Isolamento Social , Animais , Canabinoides/administração & dosagem , Canabinoides/farmacologia , Proteínas de Ligação a DNA/metabolismo , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Knockout , Neurotransmissores/genética , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares , Dor/genética , Dor/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Ratos , Ratos Wistar , Receptor Muscarínico M1/metabolismo , Receptor Muscarínico M5/metabolismo , Receptores de LDL/metabolismo , Esquizofrenia/metabolismo , Canais de Cátion TRPV/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Both anandamide and adenosine have significant roles in pain mechanisms, but no data are available concerning their interaction at the spinal level. The goal of this study was to determine how adenosine and the adenosine receptor antagonist caffeine affect the antinociceptive effect of anandamide. The pain sensitivity was assessed by the acute tail-flick test and by paw withdrawal test after carrageenan-induced inflammation. The substances were administered intrathecally to male Wistar rats. Anandamide alone (1, 30 and 100 microg) dose-dependently decreased the hyperalgesia, however it had low potency in the tail-flick test. Neither adenosine (100 microg) nor caffeine (400 microg) alone changed the pain sensitivity markedly. Their combination caused a short-lasting antihyperalgesia, but it did not influence the tail-flick latency. Both adenosine and caffeine decreased the antihyperalgesic potential of 100 microg anandamide, while adenosine-caffeine pretreatment temporarily enhanced its effect. As regards acute heat pain sensitivity, no combination with anandamide influenced the effect of anandamide. These findings provide new data concerning the interaction between two endogenous ligands and caffeine. Since these substances may exert effects on several receptors and/or systems, their interaction in vivo must be very complex and the net outcome after their coadministration could not been predicted from the in vitro results.
Assuntos
Adenosina/farmacologia , Analgésicos , Ácidos Araquidônicos/farmacologia , Dor/tratamento farmacológico , Alcamidas Poli-Insaturadas/farmacologia , Adenosina/administração & dosagem , Animais , Ácidos Araquidônicos/administração & dosagem , Cafeína/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Endocanabinoides , Temperatura Alta , Inflamação/complicações , Inflamação/tratamento farmacológico , Injeções Espinhais , Masculino , Dor/etiologia , Dor/psicologia , Medição da Dor/efeitos dos fármacos , Alcamidas Poli-Insaturadas/administração & dosagem , Antagonistas de Receptores Purinérgicos P1 , Ratos , Ratos Wistar , Tempo de ReaçãoRESUMO
A very interesting and rapidly developing field of pain research is related to the roles of different endogenous ligands. This study determined the antinociceptive interactions of triple and quadruple combinations of different endogenous ligands (endomorphin-1, adenosine, agmatine and kynurenic acid) on carrageenan-induced inflammatory pain model at the spinal level. Intrathecal infusion (60 min) of these drugs alone, in double, triple or quadruple combinations, was followed by a 60-min observation period. During the infusion, antihyperalgesic effect of 0.3 microg/min endomorphin-1 was higher in the triple combinations than those in the double combinations. After cessation of drug administration, only the combination of 0.3 microg/min endomorphin-1, 1 microg/min agmatine, and 0.3 microg/min adenosine was more effective than the double combinations. In quadruple combinations, the antinociceptive effects of both 0.1 and 0.3 microg/min endomorphin-1 were significantly potentiated by the otherwise ineffective triple combination of adenosine, agmatine, and kynurenic acid. No side effects could be observed at these doses. These results demonstrate that triple and quadruple combinations of these endogenous ligands caused more effective antihyperalgesia compared with double combinations. Accordingly, the doses of these substances could be further reduced, thus, reinforcing the view that complex activation and/or inhibition of different systems can be sufficiently effective in blocking nociception without adverse effects. Because all of these drugs had effects on various receptors and systems, the possible types of these interactions were discussed.
Assuntos
Analgésicos/farmacologia , Dor , Medula Espinal/fisiologia , Adenosina/administração & dosagem , Adenosina/farmacocinética , Adenosina/farmacologia , Agmatina/administração & dosagem , Agmatina/farmacocinética , Agmatina/farmacologia , Analgésicos/administração & dosagem , Analgésicos/farmacocinética , Animais , Área Sob a Curva , Modelos Animais de Doenças , Combinação de Medicamentos , Injeções Espinhais , Ácido Cinurênico/administração & dosagem , Ácido Cinurênico/farmacocinética , Ácido Cinurênico/farmacologia , Ligantes , Masculino , Atividade Motora/efeitos dos fármacos , Oligopeptídeos/administração & dosagem , Oligopeptídeos/farmacocinética , Oligopeptídeos/farmacologia , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas G/efeitos dos fármacos , Receptores Acoplados a Proteínas G/fisiologia , Receptores Opioides mu/efeitos dos fármacos , Receptores Opioides mu/fisiologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/fisiopatologiaRESUMO
Rehabilitation including physiotherapy is an important part of the treatment used to help improve the quality of life of patients with cystic fibrosis (CF). The aim of this study was to determine the value of the breath-hold time as an index of exercise tolerance in patients with CF. Eighteen patients in different states of CF were included. The breath-hold time was measured in all patients. The fitness level was assessed by means of a progressive exercise test on a cycle-ergometer. During the test, oxygen uptake (VO(2)) and carbon dioxide elimination (VCO(2)) were measured breath by breath. The VO(2) and working capacity (WC) were computed at the anaerobic threshold (AT) and at peak. Duration of breath-hold was 24.7 +/- 2.87 (mean +/- SEM) seconds, varying between 10 and 58. The breath-hold time (BHT) displayed a significant correlation with VO(2) (r = 0.898), WC (r = 0.899) at the AT, and the peak VO(2) (r = 0.895). Regression equations were: VO(2) at the AT (ml/kg) = 5.53 + 0.42 x BHT and WC at the AT (watt/kg) = 0.56 + 0.38 x BHT Our results suggest that the voluntary breath-hold time might be a useful index for prediction of the exercise tolerance of CF patients.
Assuntos
Fibrose Cística/fisiopatologia , Tolerância ao Exercício/fisiologia , Respiração , Adolescente , Adulto , Limiar Anaeróbio , Teste de Esforço , Feminino , Humanos , Masculino , Consumo de OxigênioRESUMO
Adenosine, agmatine and kynurenic acid are endogenous ligands acting on different (e.g. adenosine, NMDA, alpha(2)-adrenergic and imidazoline) receptors with a potential role in nociception at the spinal level. Their antinociceptive effects have already been investigated as monotherapy, but only a few studies have reported on their effects on the potency of other drugs. The purpose of the present study was carried out to analyse their interactions during continuous intrathecal co-administration in a carrageenan-induced thermal hyperalgesia model in rats. A paw withdrawal test was used for nociceptive testing. The intrathecal infusion (60 min) of these three drugs was administered alone or in combinations (kynurenic acid+adenosine or agmatine; adenosine+agmatine), which was followed by an additional 60-min observation period. Kynurenic acid alone was ineffective, while adenosine and agmatine alone caused a slight increase in pain threshold. However, independently of the applied doses all of the combinations significantly (p<0.05) increased the paw withdrawal latencies on the inflamed side during and after the infusion, but were almost ineffective on the normal side. The adenosine+kynurenic acid combination was the most effective: namely, that it relieved thermal hyperalgesia in all the applied dose combinations. Treatment with the kynurenic acid-containing combinations also caused dose-dependent side-effects (motor impairment and excitation), despite the fact that monotherapy with kynurenic acid in the applied dose (0.1 microg/min) did not result in adverse effects.
Assuntos
Adenosina/administração & dosagem , Agmatina/administração & dosagem , Analgésicos/administração & dosagem , Ácido Cinurênico/administração & dosagem , Limiar da Dor/efeitos dos fármacos , Animais , Carragenina , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Sinergismo Farmacológico , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Hiperalgesia/induzido quimicamente , Injeções Espinhais , Ligantes , Masculino , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacosRESUMO
UNLABELLED: Recently, a series of endogenous ligands related to inhibition of sensory transduction of noxious stimuli at the spinal level has been described, including endomorphins, agmatine, and adenosine, which act on different receptors; however, little data exist concerning their effect during continuous administration or their interactions. In this study, we investigated the antinociceptive properties of continuously administered (for 60 min) adenosine and agmatine on carrageenan-induced thermal hyperalgesia by means of a thermal paw withdrawal test in awake rats. The possible interaction between endomorphin-1 and adenosine or agmatine was also determined. Continuous administration of adenosine (0.3-3 microg/min) did not influence the paw withdrawal latencies of the normal or inflamed paws during the infusion but in larger doses it resulted in a significant increase in latencies after the cessation of the infusion. Agmatine (0.3-3 microg/min) dose-dependently decreased the hyperalgesia, but the largest dose caused a temporary excitation in 50% of animals. The continuous administration of adenosine or agmatine (3 micro g/min) potentiated and prolonged the antinociceptive effect of endomorphin-1 (1 microg/min). Our results revealed that adenosine and agmatine have a small antinociceptive efficacy during continuous intrathecal administration but that both potentiate the effect of endomorphin-1. These data suggest that the combination of these endogenous ligands might represent novel targets for the therapeutic modulation of pain; however, the systematic examination of side effects is essential. IMPLICATIONS: Adenosine and agmatine have little antinociceptive efficacy during continuous intrathecal administration, as shown by the inflammatory pain test in rats, but both potentiate the effect of endomorphin-1. These data suggest that the combination of these endogenous ligands might represent novel targets for the therapeutic modulation of pain; however, the systematic examination of side effects is essential.
Assuntos
Adenosina/farmacologia , Agmatina/farmacologia , Analgésicos Opioides/farmacologia , Analgésicos/farmacologia , Oligopeptídeos/farmacologia , Adenosina/administração & dosagem , Agmatina/administração & dosagem , Analgésicos Opioides/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Interações Medicamentosas , Injeções Espinhais , Ligantes , Masculino , Oligopeptídeos/administração & dosagem , Ratos , Ratos WistarRESUMO
We evaluated the modulation by Na+,K+-ATPase inhibitors of morphine-induced antinociception in the tail-flick test and [3H]naloxone binding to forebrain membranes. The antinociception induced by morphine (1-32 mg/kg, s.c.) in mice was dose-dependently antagonized by ouabain (1-10 ng/mouse, i.c.v.), which produced a significant shift to the right of the morphine dose-response curve. The i.c.v. administration of three Na+,K+-ATPase inhibitors (ouabain at 0.1-100, digoxin at 1-1000, and digitoxin at 10-10000 ng/mouse) dose-dependently antagonized the antinociceptive effect of morphine (4 mg/kg, s.c.) in mice, with the following order of potency: ouabain > digoxin > digitoxin. This effect cannot be explained by any interaction at opioid receptors, since none of these Na+,K+-ATPase inhibitors displaced [3H]naloxone from its binding sites, whereas naloxone did so in a concentration-dependent manner. The antinociception induced by morphine (5 mg/kg, s.c.) in rats was antagonized by the i.c.v. administration of ouabain at 10 ng/rat, whereas it was not significantly modified by intrathecally administered ouabain (10 and 100 ng/rat). These results suggest that the activation of Na+,K+-ATPase plays a role in the supraspinal, but not spinal, antinociceptive effect of morphine.
Assuntos
Analgesia , Analgésicos Opioides/farmacologia , Morfina/farmacologia , Ouabaína/farmacologia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Animais , Interações Medicamentosas , Camundongos , Naloxona/farmacologia , Dor/prevenção & controle , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/fisiologiaRESUMO
The goal of this study was to investigate the effects of endomorphin-1 on Na(+),K(+)-ATPase activity in mouse brain synaptosome in vitro, and its antinociceptive interaction with the Na(+),K(+)-ATPase inhibitor ouabain. Endomorphin-1 (0.1 nM-10 microM) produced a concentration-dependent (EC(50): 43.19 nM, CI: 23.38-65.71 nM, E(max): 25.86%, CI: 24.53-27.20%), naloxone-reversible increase of the synaptosomal Na(+),K(+)-ATPase activity. The intrathecally (i.t.) administered endomorphin-1 (2-20 microg) produced a dose-dependent short-lasting increase in the tail-flick latency. Ouabain itself (1-1000 ng, i.t.) did not cause antinociception. Treatment with 10 ng ouabain significantly decreased the antinociceptive effect of 2 microg endomorphin-1, but none of the other combinations did significantly differ from the endomorhin-1-treated groups. These data indicate that endomorphin-1 increases the activity of Na(+),K(+)-ATPase in vitro but this effect may play a weak role in the antinociception induced by intrathecal endomorphin-1.