RESUMEN
The treatment of oral and maxillofacial infections is based on a recognized algorithm that may require modification under the influence of various local and systemic factors. The aim of this study was to present a comprehensive and microbiological profile of oral and maxillofacial infections, and explore possible correlations between the course of an infection and selected systemic factors based on the medical records of 329 patients affected by the disease. We identified most common clinical, demographic, bacterial, and laboratory parameters specific for these infections. There were statistically significant differences in Erythrocyte Sedimentation Rate, number of accompanying diseases, otalgia, dyspnea, and speech difficulties occurrence and neck space involvement between diabetic and non-diabetic patients. The duration of hospitalization and accompanying diseases correlated positively with the patient age and white blood cell count, and C-reactive protein value negatively correlated with age. The primary cause of infections, age, and comorbid diseases can modify the infection course and increase the risk of developing serious complications. It confirms the need for effective and targeted bacterial treatment in the early stages of infections. Age and general diseases are the most important systemic factors determining the infection symptoms and laboratory parameters assessing the severity of the inflammatory process.
RESUMEN
The number of studies on the subject of effects of zirconium dioxide (ZrO2) nanoparticles addition on the mechanical parameters of polymethyl methacrylate (PMMA) is still very limited. Therefore, in this research, the authors wanted to assess PMMA modified with the nano-ZrO2 additive in terms of changes in flexural, impact and tensile strength values in relation to PMMA without such component. A systematic review and meta-analysis were performed to evaluate the effect of incorporating nano-ZrO2 into PMMA on individual types of material strength. The obtained numerical data were tabulated and analyzed in the search for percentage changes in those parameters. It was then calculated for each set and the procured model was examined using residual sum of squares (RSS) to assess the discrepancy between the data and the estimation model whilst mean absolute deviation (MAD) was employed to determine robustness. The results of the systematic review were composed of data obtained from individual studies presented in eight independent articles. Overall, the addition of nano-ZrO2 increases the flexural strength of the composite with the PMMA matrix depending on the size of the ZrO2 grains administered. Unfortunately, these conclusions are based on a very limited amount of research and require further verification, especially regarding tensile strength.
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Pharmacotherapy with two antiepileptic drugs in combination is usually prescribed to epilepsy patients with refractory seizures. The choice of antiepileptic drugs in combination should be based on synergistic cooperation of the drugs with respect to suppression of seizures. The selection of synergistic interactions between antiepileptic drugs is challenging issue for physicians, especially, if 25 antiepileptic drugs are currently available and approved to treat epilepsy patients. The aim of this study was to determine all possible interactions among 5 second-generation antiepileptic drugs (gabapentin (GBP), lacosamide (LCM), levetiracetam (LEV), pregabalin (PGB) and retigabine (RTG)) in the 6-Hz corneal stimulation-induced seizure model in adult male albino Swiss mice. The anticonvulsant effects of 10 various two-drug combinations of antiepileptic drugs were evaluated with type I isobolographic analysis associated with graphical presentation of polygonogram to visualize the types of interactions. Isobolographic analysis revealed that 7 two-drug combinations of LEV+RTG, LEV+LCM, GBP+RTG, PGB+LEV, GBP+LEV, PGB+RTG, PGB+LCM were synergistic in the 6-Hz corneal stimulation-induced seizure model in mice. The additive interaction was observed for the combinations of GBP+LCM, GBP+PGB, and RTG+LCM in this seizure model in mice. The most beneficial combination, offering the highest level of synergistic suppression of seizures in mice was that of LEV+RTG, whereas the most additive combination that protected the animals from seizures was that reporting additivity for RTG+LCM. The strength of interaction for two-drug combinations can be arranged from the synergistic to the additive, as follows: LEV+RTG > LEV+LCM > GBP+RTG > PGB+LEV > GBP+LEV > PGB+RTG > PGB+LCM > GBP+LCM > GBP+PGB > RTG+LCM.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Electrochoque/efectos adversos , Convulsiones/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Quimioterapia Combinada , Gabapentina/uso terapéutico , Lacosamida/uso terapéutico , Levetiracetam/uso terapéutico , Masculino , Ratones , Fuerza Muscular , Convulsiones/etiologíaRESUMEN
BACKGROUND: Launching polytherapy with two or three antiseizure drugs (ASDs) in patients with epilepsy is still problematic. The choice of ASDs to combine them together is usually based on clinicians' experience and it requires knowledge about mechanisms of action of the studied ASDs and their drug-drug interactions, whose nature may be favorable, neutral or unfavorable. To characterize three-drug interaction among lacosamide (LCM), lamotrigine (LTG) and valproate (VPA), the type I isobolographic analysis was used. The antiseizure effects of three-drug combination were analyzed in a model of maximal electroshock-induced seizures (MES) in albino Swiss mice. MATERIALS AND METHODS: The seizure activity in mice was evoked by alternating current stimulation (25 mA, 500 V, 50 Hz, 0.2 s). Both, the type I isobolographic analysis and the test of parallelism of dose-response effects of the ASDs were used so as to properly classify interaction among three ASDs, administered in a fixed ratio combination of 1:1:1. RESULTS: The three-drug mixture of LCM, LTG and VPA at the fixed ratio of 1:1:1 protected the experimental mice from MES-induced seizures; however, the reported interaction was sub-additive (antagonistic; p < 0.01) with isobolography. CONCLUSION: The antagonistic pharmacodynamic interaction among LCM, LTG and VPA in the MES test in mice cannot be transferred to clinical settings and this unfavorable combination should not be recommended for patients with epilepsy.
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Anticonvulsivantes/farmacología , Lacosamida/farmacología , Lamotrigina/farmacología , Convulsiones/tratamiento farmacológico , Convulsiones/terapia , Ácido Valproico/farmacología , Animales , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas/fisiología , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Electrochoque/métodos , Epilepsia/tratamiento farmacológico , Epilepsia/terapia , Masculino , RatonesRESUMEN
Accumulating experimental evidence indicates that some recently licensed antiarrhythmic drugs, including dronedarone (a multichannel blocker) play a crucial role in initiation of seizures in both, in vivo and in vitro studies. Some of these antiarrhythmic drugs elevate the threshold for maximal electroconvulsions and enhance the anticonvulsant potency of classical antiepileptic drugs in preclinical studies. This study was aimed at determining the influence of dronedarone (an antiarrhythmic drug) on the anticonvulsant potency of four novel antiepileptic drugs (lacosamide, lamotrigine, pregabalin and topiramate) in the maximal electroshock-induced seizure model in mice. To exclude any potential pharmacokinetic contribution of dronedarone to the observed interactions, total brain concentrations of antiepileptic drugs were measured. Dronedarone (50 mg/kg, i.p.) significantly enhanced the anticonvulsant potency of lamotrigine, by reducing its ED50 value from 7.67 mg/kg to 4.19 mg/kg (P < 0.05), in the maximal electroshock-induced seizure test in mice. On the contrary, dronedarone (50 mg/kg, i.p.) did not affect the anticonvulsant properties of lacosamide, pregabalin or topiramate in the maximal electroshock-induced seizure test in mice. Measurement of total brain concentrations of lamotrigine revealed that dronedarone did not significantly alter total brain concentrations of lamotrigine in experimental animals. Additionally, the combination of dronedarone with pregabalin significantly impaired motor coordination in animals subjected to the chimney test. In contrast, the combinations of other studied antiepileptic drugs with dronedarone had no negative influence on motor coordination in mice. It is advisable to combine dronedarone with lamotrigine to enhance the anticonvulsant potency of the latter drug. The combinations of dronedarone with lacosamide, pregabalin and topiramate resulted in neutral interactions in the maximal electroshock-induced seizure test in mice. However, a special caution is advised to patients receiving both, pregabalin and dronedarone due to some possible adverse effects that might occur with respect to motor coordination.
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Dronedarona/administración & dosificación , Lacosamida/administración & dosificación , Lamotrigina/administración & dosificación , Pregabalina/administración & dosificación , Convulsiones/tratamiento farmacológico , Topiramato/administración & dosificación , Animales , Antiarrítmicos/administración & dosificación , Antiarrítmicos/farmacocinética , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/farmacocinética , Modelos Animales de Enfermedad , Dronedarona/farmacocinética , Sinergismo Farmacológico , Quimioterapia Combinada , Lacosamida/farmacocinética , Lamotrigina/farmacocinética , Masculino , Ratones , Pregabalina/farmacocinética , Convulsiones/metabolismo , Topiramato/farmacocinéticaRESUMEN
BACKGROUND: To assess the effects of 5-(3-chlorobenzyl)-4-hexyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (TP427) on the protective anticonvulsant action of four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) in the tonic-clonic seizure model in mice, an isobolographic transformation of data was used. METHODS: Electrically-induced tonic-clonic seizures were experimentally evoked in adult male albino Swiss mice. The anticonvulsant effects of TP427, when used singly, were determined by the calculation of the threshold increasing the dose by 20% (TID20 value). The influence of TP427 on the anticonvulsant potency of four various classical antiepileptic drugs was determined with a subthreshold method. Types of interactions between drugs were determined using the isobolographic transformation of data. Additionally, total brain antiepileptic drug concentrations were measured. RESULTS: TP427, when administered separately, significantly increased the threshold for electroconvulsions. The experimentally determined TID20 value for TP427 was 11.71 mg/kg. Moreover, TP427 (10 mg/kg) significantly increased the anticonvulsant activity of valproate (p < 0.01), but not that of carbamazepine, phenobarbital or phenytoin in the mouse tonic-clonic seizure model. Isobolographic transformation of data confirmed that the interaction between TP427 and valproate was synergistic. Pharmacokinetic study revealed that TP427 increased total brain valproate concentrations, and had no impact on total brain concentrations of carbamazepine, phenobarbital or phenytoin in mice. CONCLUSION: The synergistic interaction between TP427 and valproate in the mouse tonic-clonic seizure model might occur favorable for epilepsy patients in future. The combinations of TP427 with carbamazepine, phenobarbital and phenytoin were additive in the mouse tonic-clonic seizure model and also deserves clinical attention.
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Anticonvulsivantes/farmacología , Convulsiones/tratamiento farmacológico , Ácido Valproico/farmacología , Animales , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/farmacocinética , Carbamazepina/administración & dosificación , Carbamazepina/farmacocinética , Carbamazepina/farmacología , Modelos Animales de Enfermedad , Interacciones Farmacológicas , Sinergismo Farmacológico , Quimioterapia Combinada , Masculino , Ratones , Fenobarbital/administración & dosificación , Fenobarbital/farmacocinética , Fenobarbital/farmacología , Fenitoína/administración & dosificación , Fenitoína/farmacocinética , Fenitoína/farmacología , Convulsiones/fisiopatología , Ácido Valproico/administración & dosificación , Ácido Valproico/farmacocinéticaRESUMEN
Increasing evidence indicates that some antiarrhythmic drugs play a pivotal role in seizures, not only in vivo studies on animals, but also in clinical trials. Some of these antiarrhythmic drugs potentiate or alleviate the anticonvulsant action of the classical antiepileptic drugs. The aim of this study was to determine the influence of dronedarone (DRO-a multichannel blocker belonging to the class III of antiarrhythmic drugs) on the anticonvulsant effects of four standard antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) in the tonic-clonic seizure model in mice. Potential acute adverse effects exerted by the antiepileptic drugs combined with DRO were evaluated in three behavioral tests (chimney, grip-strength and passive avoidance). To confirm the nature of interaction, total brain concentrations of antiepileptic drugs were measured. DRO (50 mg/kg, i.p.) significantly reduces the anticonvulsant potency of phenytoin (P < 0.05), having no impact on that of carbamazepine, phenobarbital and valproate in the tonic-clonic seizure model in mice. DRO (50 mg/kg) neither changed total brain concentrations of phenytoin in mice, nor affected normal behavior in experimental animals subjected to the chimney, grip-strength and passive avoidance tests. In conclusion, DRO should not be combined with phenytoin because it reduced the anticonvulsant effects of the latter drug in experimental animals. The combined administration of DRO with carbamazepine, phenobarbital and valproate resulted in neutral interaction between these drugs in the tonic-clonic seizure model in mice.
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Antiarrítmicos/farmacología , Anticonvulsivantes/farmacología , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Dronedarona/farmacología , Interacciones Farmacológicas , Convulsiones/tratamiento farmacológico , Animales , Carbamazepina/farmacología , Modelos Animales de Enfermedad , Masculino , Fenobarbital/farmacología , Fenitoína/farmacología , Ácido Valproico/farmacologíaRESUMEN
The aim of this study was to determine the effect of WIN 55,212-2 mesylate (WIN - a non-selective cannabinoid CB1 and CB2 receptor agonist) on the protective action of four second-generation antiepileptic drugs (lamotrigine, oxcarbazepine, pregabalin and topiramate) in the mouse maximal electroshock seizure model. Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2s stimulus duration) delivered via auricular electrodes. Drug-related adverse effects were ascertained by use of the chimney test (evaluating motor performance), the step-through passive avoidance task (assessing long-term memory) and the grip-strength test (evaluating skeletal muscular strength). Total brain concentrations of antiepileptic drugs were measured by high-pressure liquid chromatography to ascertain any pharmacokinetic contribution to the observed antiseizure effect. Results indicate that WIN (5mg/kg, i.p.) significantly enhanced the anticonvulsant action of lamotrigine (P<0.05), pregabalin (P<0.001) and topiramate (P<0.05), but not that of oxcarbazepine in the maximal electroshock-induced tonic seizure test in mice. Furthermore, none of the investigated combinations of WIN with antiepileptic drugs were associated with any concurrent adverse effects with regards to motor performance, long-term memory or muscular strength. Pharmacokinetic characterization revealed that WIN had no impact on total brain concentrations of lamotrigine, oxcarbazepine, pregabalin and topiramate in mice. These preclinical data would suggest that WIN in combination with lamotrigine, pregabalin and topiramate is associated with beneficial anticonvulsant pharmacodynamic interactions in the maximal electroshock-induced tonic seizure test.