Assessment of the antinociceptive and ulcerogenic activity of the tapentadol-diclofenac combination in rodents.

Preclinical Research & Development The objective of the present study was to evaluate the tapentadol-diclofenac combination in three dose-ratios in the mouse acetic acid-induced visceral pain and their ulcerogenic activity on the stomachal mucous. Dose-response curves were generated for tapentadol, diclofenac, and their combination in the acetic acid-induced writhing test in mice. Moreover, the stomachs of animals were surgically removal and gastrointestinal ulcerogenic action of the combination was assessed. The isobolographic analysis, interaction index, and ANOVA were used to analyze the data. The isobolographic analysis and interaction index showed a similar antinociceptive activity for the three combinations of the analgesic mixture. Moreover, tapentadol and the proportions 1:1 or 3:1 of the analgesic combination caused a mild gastrointestinal damage. These data indicate that the systemic co-administration of tapentadol and diclofenac produced a synergistic interaction in the acetic acid-induced visceral pain test with an acceptable gastric damage profile in mice.

Participation of ATP-sensitive K+ channels and µ-opioid receptors in the antinociceptive synergism of the paracetamol-tapentadol co-administration in the formalin-induced pain assay in mice.

Preclinical Research & Development The purpose of this study was to assess the interaction and mechanisms of action of the paracetamol-tapentadol combination in the formalin-induced pain model in mice. Paracetamol (56.23-562.3 mg/kg, i.p.) or tapentadol (1-10 mg/kg, i.p.) were administered 15 min prior the intraplantar injection of formalin. The ED50 value of each drug was determined through the dose-response curves. The ED50 values were used to calculate the combinations in three fixed proportions (1:1, 1:3, and 3:1). Naloxone (1 and 5 mg/kg, i.p.), L-NAME (3 mg/kg, i.p.), or glibenclamide (10 mg/kg, i.p.) were administered before the combination of drugs to evaluate the antinociceptive mechanisms of action. The results showed that the combination 1:1 and paracetamol3-tapenadol1 ratios produced additive effects, whereas the paracetamol1-tapentadol3 proportion showed an antinociceptive synergistic interaction. Moreover, naloxone and glibenclamide reversed the antinociceptive activity of the paracetamol-tapentadol mixture. Our results indicate that the paracetamol-tapentadol combination produces an antinociceptive synergistic interaction with the possible participation of ATP-sensitive K+ channels and µ-opioid receptors in the second phase of the formalin-induced pain model in mice.

Synergism between Naproxen and Rutin in a Mouse Model of Visceral Pain.

Preclinical Research The aim of the present study was to evaluate the antinociceptive interaction between naproxen and the glycoside flavonoid, rutin in the acetic acid-induced writhing test in mice. Naproxen (5, 20, 50, and 100 mg/kg p.o.) or rutin (10, 25, 50, and 100mg/kg p.o.) were administered 60 min before the intraperitoneal administration with acetic acid. The dose-response curve of each individual compound and the experimental effective dose 50 (ED50 ) value were obtained to determinate different proportions of the combinations between the two compounds (naproxen-rutin 1:1, 3:1, and 3:1) in the writhing test. The results indicated a synergistic antinociceptive interaction between two drugs with different mechanism of action, naproxen and rutin in all the combinations. Drug Dev Res 78 : 184-188, 2017. © 2017 Wiley Periodicals, Inc.

The Antinociceptive Effect of a Tapentadol-Ketorolac Combination in a Mouse Model of Trigeminal Pain is Mediated by Opioid Receptors and ATP-Sensitive K+ Channels.

Preclinical Research The aim of the present study was to evaluate the antinoceptive interaction between the opioid analgesic, tapentadol, and the NSAID, ketorolac, in the mouse orofacial formalin test. Tapentadol or ketorolac were administered ip 15 min before orofacial formalin injection. The effect of the individual drugs was used to calculate their ED50 values and different proportions (tapentadol-ketorolac in 1:1, 3:1, and 1:3) were assayed in the orofacial test using isobolographic analysis and interaction index to evaluate the interaction between the drugs. The combination showed antinociceptive synergistic and additive effects in the first and second phase of the orofacial formalin test. Naloxone and glibenclamide were used to evaluate the possible mechanisms of action and both partially reversed the antinociception produced by the tapentadol-ketorolac combination. These data suggest that the mixture of tapentadol and ketorolac produces additive or synergistic interactions via opioid receptors and ATP-sensitive K+ channels in the orofacial formalin-induced nociception model in mice. Drug Dev Res 78 : 63-70, 2017. © 2016 Wiley Periodicals, Inc.

Isobolographic Analysis of the Interaction Between Tapentadol and Ketorolac in a Mouse Model of Visceral Pain.

Preclinical Research The aim of this experimental assay was to assess the antinociceptive interaction between tapentadol and ketorolac in the acetic acid-induced writhing model in mice. Tapentadol (5.62-31.6 mg/kg ip) or ketorolac (5.62-31.6 mg/kg ip) were administered 15 min before the acetic acid administration. The ED50 values of the individual drugs were determined and different proportions (tapentadol-ketorolac in 1:1, 3:1, and 1:3) were assayed in combination in the writhing test. Isobolographic analysis and the interaction index demonstrated an antinociceptive synergistic interaction between tapentadol and ketorolac in all combination. Thus, the experimental ED50 values were lower when compared with their theoretical ED50 values. These data suggest that the tapentadol-ketorolac combination produces an antinociceptive synergistic interaction in the mouse acetic acid-induced writhing model. Drug Dev Res 77 : 187-191, 2016. © 2016 Wiley Periodicals, Inc.

Involvement of nitric oxide and ATP-sensitive potassium channels in the peripheral antinoceptive action of a tramadol-dexketoprofen combination in the formalin test.

Systemic coadministration of tramadol and dexketoprofen can produce antinociceptive synergism in animals. There has been only limited evaluation of this drug combination in the peripheral nervous system in terms of the antinociceptive interaction and its mechanisms. The aim of the present study was to evaluate the peripheral antinociceptive interaction between tramadol and dexketoprofen in the formalin test and the involvement of the nitric oxide (NO)-cyclic guanosine monophosphate pathway and ATP-sensitive K(+) channels. Different doses of tramadol or dexketoprofen were administered locally to the formalin-injured mouse paw and the antinociceptive effect evaluated. ED50 values were calculated for both drugs alone and in combination. Coadministration of tramadol and dexketoprofen produced an antinociceptive synergistic interaction during the second phase of the formalin test. Pretreatment with NO antagonists, including l-NG-nitroarginine methyl ester and 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one, or the ATP-sensitive K(+) channel antagonist glibenclamide reversed the antinociceptive synergistic effect of the tramadol-dexketoprofen combination, suggesting that NO and ATP-sensitive K(+) channels were involved.

Dactylopius opuntiae [Cockerell] Could Be a Source of Antioxidants for the Preservation of Beef Patties.

Dactylopius opuntiae is an insect pest that contains at least carminic acid, which has antioxidant properties. Since there is a relationship between the antioxidant ability and preservative action of compounds applied to meat products, the purpose of this study was to evaluate the antioxidant activity and usefulness of a D. opuntiae extract for beef patty preservation. The insects were bred and processed to obtain a liquid extract. For the extract, its carminic acid content, antioxidant activity against two free radicals, and actions on food quality parameters were determined. The D. opuntiae dry powder contained 2.91% w/w carminic acid, while the liquid extract exhibited an IC50 value of 3437.8 ± 67.8 and 19633.0 ± 674.5 µg/mL against the DPPH and ABTS radicals. Nevertheless, these antioxidant actions were lower than those found in a D. coccus extract. The D. opuntiae extract improved in a short time the redness and yellowness, eliminated the unfavorable effect of their vehicle on the MetMb level, and greatly reduced the TBARS formation. For the first time, an extract of D. opuntiae was applied to beef patties, and its beneficial antioxidant action on meat acceptance parameters was confirmed, which has potential commercial applications.

Pre-emptive analgesic effectiveness of meloxicam versus tramadol after mandibular third molar surgery: a pilot study.

PURPOSE: To compare the pre-emptive analgesic effectiveness of 15 mg of meloxicam and 50 mg of tramadol after mandibular third molar surgery. PATIENTS AND METHODS: This pilot study was a double-blind, randomized, parallel-group clinical trial. The patients were randomized into 2 treatment groups, each with 15 patients, by use of a series of random numbers: group A was administered 15 mg of meloxicam intramuscularly (IM) 50 minutes before the surgery and group B was given 50 mg of tramadol IM 50 minutes before the surgery. We evaluated pain intensity, analgesic consumption, swelling, and trismus. RESULTS: The group receiving 15 mg of meloxicam IM showed differences in pain intensity evaluated by the area under the curve of the visual analog scale and total analgesic consumption when compared with the group receiving 50 mg of tramadol IM. CONCLUSION: The patients receiving 15 mg of preoperative meloxicam had less pain intensity and total analgesic consumption than those receiving 50 mg of preoperative tramadol.

Preemptive analgesic effectiveness of oral ketorolac plus local tramadol after impacted mandibular third molar surgery.

OBJECTIVE: The aim of this study was to compare preemptive analgesia of oral ketorolac plus submucous local placebo with oral ketorolac plus submucous local tramadol after impacted mandibular third molar surgery. STUDY DESIGN: A double-blind, randomized, placebo-controlled clinical trial was conducted. Patients were randomized into two treatment groups (n = 15 per group): group A, oral ketorolac 10 mg, 30 minutes before surgery plus submucous local placebo (1 mL saline solution); group B, oral ketorolac 10 mg, 30 minutes before surgery plus submucous local tramadol (50 mg diluted in 1 mL saline solution). We evaluated the intensity of pain, time for the first analgesic rescue medication, and total analgesic consumption. RESULTS: Pain intensity, number of patients requiring analgesic rescue medication, number of patients in each group not requiring analgesic rescue medication, and total analgesic consumption showed statistical significance. CONCLUSIONS: Preemptive use of oral ketorolac plus submucous local tramadol is an alternative treatment for acute pain after surgical removal of an impacted mandibular third molar.

Partial traumatic amputation of an upper limb with excellent functional recovery: A 13-year follow-up clinical case.

Introducción: Se han publicados pocos informes sobre el seguimiento a largo plazo de la reparación quirúrgica de una amputación parcial. Algunos estudios de largo plazo han registrado tasas similares de discapacidad entre los pacientes con amputaciones y los sometidos a operación reconstructiva. Objetivo: Informar un caso clínico de una amputación traumática parcial de una extremidad superior con recuperación funcional después de 13 años de seguimiento. Caso clínico: Paciente masculino de ocho años con traumatismo grave en la extremidad superior izquierda, desprendimiento de los músculos bíceps y tríceps y una fractura diafisaria oblicua del húmero distal. La fractura se fijó de manera transitoria con alambres de Kirschner de 2.0 mm, seguido de inmovilización con aparato de Sarmiento y al final se realizó reducción abierta y fijación interna con placa de compresión dinámica de 3.5 mm. La integridad muscular y neurovascular permitió la reparación microquirúrgica del nervio radial y la rehabilitación neuromuscular. Conclusiones: Este informe clínico representa un caso de una recuperación funcional excelente atestiguada a través de un periodo de seguimiento de 13 años.

Introduction: There are just a few reports that deal with long-term outcomes of a partial amputation surgical repair. Long-term studies have reported similar rates of disability among patients with amputations and those that have been undergoing reconstructive surgery. Objective: The purpose of this report is describing a clinical case of a patient with partial traumatic amputation of an upper limb with an excellent functional recovery after 13 years of follow-up. Clinical case: The case of an 8 year old male patient with severe trauma to the upper left limb is described. The lesions included an oblique diaphyseal open fracture of the distal region of the humerus, along with detachment of the biceps and triceps muscles. The fracture was fixed transiently with 2.0 mm Kirschner's wire followed by immobilization with Sarmiento's brace, and finally, open reduction and internal fixation with a 3.5 mm dynamic compression plate were performed. The muscular and neurovascular integrity allowed microsurgical repair of the radial nerve and neuromuscular rehabilitation. Conclusion: This clinical report represents a case with an excellent functional recovery witnessed through a 13-year follow-up period.

[Combination of noise plus weight-bearing accelerates consolidation time in tibial shaft fractures: A preliminary report]. / La combinación de ruido más carga de peso acelera la consolidación en las fracturas de la diáfisis tibial: Un informe preliminar.

Introduction: Long bones fractures are responsible for prolonged periods of incapacity and economic losses. New therapies for shortening the time of consolidation are needed. Thus, the purpose of this clinical study was to evaluate the efficacy of noise plus weight-bearing over the bone consolidation of tibial shaft fractures. Methods: In this clinical trial, 12 patients with tibial shaft fractures were recruited during a 24-month period. Participants were treated with intramedullary nails and randomized to two groups: an experimental group and a control group. Both groups underwent a rehabilitation program consisting of two daily walking sessions with progressive weight-bearing. Simultaneously, the experimental group received a noise stimulus on the fracture site with intensities of 0.1-0.6 N and frequencies of 0.1-50 Hz. Radiographic consolidation was evaluated by Radiographic Unión Scale of Tibia. Results: X-ray consolidation was achieved at 18.6 ± 3.6 weeks and 27.2 ± 6.9 weeks, for experimental and control group, respectively (p < 0.05). Recovery of mobility ranges in the knee and ankle was faster in the experimental group than in the control group. Conclusions: This new method to stimulate fracture consolidation has the following advantages: it is effective, portable, easy to use, and inexpensive.

Introducción: Las fracturas de huesos largos son causa de períodos prolongados de incapacidad y pérdidas económicas. Se necesitan nuevas terapias para acortar el tiempo de consolidación. Por lo tanto, el objetivo de este estudio clínico fue evaluar la eficacia del ruido más el soporte de peso sobre la consolidación ósea de las fracturas de la diáfisis tibial. Método: En este ensayo clínico, 12 pacientes con fracturas de la diáfisis tibial fueron reclutados durante un período de 24 meses. Los participantes fueron tratados con clavos intramedulares y luego aleatorizados a dos grupos: un grupo experimental y un grupo control. Ambos grupos se sometieron a un programa de rehabilitación que consta de dos sesiones diarias de caminata con soporte progresivo de peso. Simultáneamente, el grupo experimental recibió un estímulo de ruido en el sitio de la fractura con intensidades de 0.1-0.6 N y frecuencias de 0.1-50 Hz. La consolidación radiográfica se evaluó mediante la escala RUST. Resultados: La consolidación radiográfica se logró a las 18.6 ± 3.6 semanas en el grupo experimental y a las 27.2 ± 6.9 semanas en el grupo control (p < 0.05). La recuperación de los rangos de movilidad en la rodilla y el tobillo fue más rápida en el grupo experimental que en el grupo control. Conclusiones: Este nuevo método para estimular la consolidación de fracturas tiene las siguientes ventajas: es eficaz, portátil, fácil de usar y económico.

Bacterial resistance and failure of clinical cure could be produced by oxidative stress in patients with diabetes or cardiovascular diseases during fluoroquinolone therapy.

Fluoroquinolone agents are used widely for the treatment of infectious diseases which are a common cause of deaths around the world. The level of oxidative stress in patients taking fluoroquinolone antibiotics has not been considered a factor to reduce the clinical efficacy of this kind of drugs. Patients with diabetes and/or cardiovascular diseases present abnormal levels of oxidative stress in the blood stream. In this regards, our hypothesis supposes that patients with diabetes and/or cardiovascular disease suffering a bacterial disease could experience a therapeutic failure and bacterial resistance when treated with fluoroquinolones. The crucial mechanism could be an inefficient blood distribution of the drug via red blood cell dysfunction induced by oxidative stress that might reduce the pharmacokinetic-pharmacodinamic ratios. In this way, we review the scientific information to support our hypothesis alongside possible implications. Additionally, this work exhibits the urgent need of studies considering these conditions for quinolone agents.

Myeloid derived suppressor cell: A new player in periodontal disease?

Periodontal disease can be initiated by a shift from a symbiotic to a dysbiotic microbial community. An increase in the recruitment of leukocytes and production of inflammatory cytokines, chemokines and oxidative stress are generated by this shift. In periodontitis, an exacerbated, poorly specific and effective inflammatory response is mounted. Moreover, failure in the inflammation resolving mechanism leads to establishment of a chronic inflammatory process, resulting in the progressive destruction of bone and soft tissue. In different diseases presenting chronic inflammation some important players of immune response are defectives. Thus, an immunosuppressive environment could be induced during chronic inflammation. Myeloid derived suppressor cells (MDSC), a heterogenic group of immature myeloid cells with potent immune suppressive activity, are increased in several acute and chronic inflammatory diseases. Dysbiosis-mediated inflammation can induce increased frequency of MDSC. In addition, mediators generated in diverse inflammatory diseases have demonstrated to promote expansion, activation and recruitment of MDSC, similar mediators have been described in periodontal disease. MDSC promote generation of nitric oxide (NO) and reactive oxygen species (ROS). Furthermore, MDSC can differentiate in functional osteoclasts. We hypothesize that MDSC are generated during periodontal disease. Review of literature evaluating this hypothesis and possible implications are assed in this work. It encourages the study of MDSC in this common disease.

Preemptive analgesic effectiveness of oral ketorolac plus local tramadol afterimpacted mandibular third molar surgery

Objective: The aim of this study was to compare preemptive analgesia of oral ketorolac plus submucous localplacebo with oral ketorolac plus submucous local tramadol after impacted mandibular third molar surgery.Study design: A double-blind, randomized, placebo-controlled clinical trial was conducted. Patients were randomizedinto two treatment groups (n = 15 per group): group A, oral ketorolac 10 mg, 30 minutes before surgeryplus submucous local placebo (1 mL saline solution); group B, oral ketorolac 10 mg, 30 minutes before surgeryplus submucous local tramadol (50 mg diluted in 1 mL saline solution). We evaluated the intensity of pain, timefor the first analgesic rescue medication, and total analgesic consumption.Results: Pain intensity, number of patients requiring analgesic rescue medication, number of patients in each groupnot requiring analgesic rescue medication, and total analgesic consumption showed statistical significance.Conclusions: Preemptive use of oral ketorolac plus submucous local tramadol is an alternative treatment for acutepain after surgical removal of an impacted mandibular third molar (AU)

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