Analgesic Efficacy and Safety of Tapentadol Immediate Release in Bunionectomy: A Meta-Analysis.

The aim of this systematic review and meta-analysis was to evaluate the analgesic effect of different doses of tapentadol immediate release (IR) and its adverse effects after a bunionectomy. Pubmed, Cochrane, Lilacs, Medline, and Imbiomed were used to identify abstracts of scientific publications related to the keywords of this systematic review (PROSPERO ID CRD42023437295). Moreover, the risk of bias in all included articles was assessed using the Cochrane Collaboration risk of bias tool. Data on the sum of pain intensity, total pain relief, global assessment, and adverse effects were extracted. The statistical method of inverse variance with means difference was used to evaluate the numerical data and the Mantel-Haenszel and Odd Ratio test to analyze the dichotomous data. In addition, the number needed to treat, the number needed to harm, and the 95% confidence intervals were calculated. A qualitative evaluation (n = 2381) was carried out according to the conclusions of the authors. Tapentadol (n = 1772) was more effective in relieving postoperative pain than the placebo (n = 609) after a bunionectomy. In addition, the analgesic efficacy of IR tapentadol (n = 1323) versus the placebo (n = 390) was evaluated in a total of 1713 patients using a global evaluation of the treatments. All three doses of IR tapentadol showed better results compared to the placebo after a bunionectomy. Finally, the adverse effects have a direct relationship with the dose, and the greatest number of adverse effects are most observed with tapentadol IR 100 mg (n = 2381). It is concluded that tapentadol IR (100 mg) leads to the best satisfaction score in this meta-analysis.

Isobolographic analysis of the ciprofloxacin-gentamicin combination against beta-lactamase-producing Staphylococcus aureus.

BACKGROUND: Bacterial multi-resistance is a serious global problem that continues to worsen over time due to multiple factors. Among these factors, it is important to highlight the clinical misuse of antibiotics and the mechanisms that microorganisms have developed to protect themselves from these drugs. In this sense, Staphylococcus aureus (S. aureus) is a pathogen that has found a way to resist many of the drugs currently in use, so infections by this bacterium represent a serious clinical problem. OBJECTIVES: The purpose of this study was to determine the type of interaction between ciprofloxacin and gentamicin against beta-lactamase-producing S. aureus using isobolographic analysis. METHODS: Ciprofloxacin (0.5-0.05 mg/mL) and gentamicin (10-1 mg/mL) were used to make concentration-dependent curves for each individual drug. Thereafter, the 50 inhibitory concentration (IC50 ) of each drug was obtained, and different proportions of the ciprofloxacin-gentamicin combination-0.5:0.5, 0.8:0.2, 0.2:0.8, 0.9:0.1, 0.1:0.9, 0.95:0.05, and 0.05:0.95-were evaluated. The isobolographic analysis and the interaction index were used to analyze the data. RESULTS: The isobolographic evaluation of the combination showed that the ratios 0.5:0.5, 0.8:0.2, 0.2:0.8, and 0.9:0.1 produced a synergistic anti-staphylococcal effect, and the 0.95:0.05 ratio induced an additive antibacterial effect. Finally, the 0.1:0.9 and 0.05:0.95 ratios of the combination presented antagonistic effects against S. aureus. On the other hand, the interaction index showed similar results to the isobolographic analysis. CONCLUSION: The isobolographic results of this in vitro assay show that the ciprofloxacin-gentamicin combination induces synergistic, additive, and antagonistic antimicrobial effects against S. aureus.

Evaluación del Efecto de un Gel con Arginina sobre el PH y Flujo Salival

RESUMEN: Se evaluó el efecto de un gel con arginina sobre el pH y flujo salival después de un uso de catorce días en mujeres con desmineralización dental leve. Se estableció un piloto de ensayo clínico controladoen el cual fueron incluidas 20 mujeres de 18 -23 años, sistémicamente sanas y con al menos un órgano dental con desmineralización ICDAS 3, dos grupos: Grupo A / sin arginina (N=10) y Grupo B/ con arginina (N=10). Se realizó una evaluación clínica y toma de una muestra de saliva no estimulada para la determinación del pH, y la medición del flujo salival al inicio y 15 días posterior a la utilización del gel. Se realizó el análisis estadístico con el programa GraphPadPrism versión 8. Una p<0,05 fue considerado como estadísticamente significativo. En ambos grupos se mantuvo el pH salival cercano a la neutralidad sin diferencias estadísticamente significativas y el flujo salival permaneció en valores normales tras la utilización del gel durante 14 días, aunque se observaron diferencias estadísticas significativas en la comparación inter-grupo. La utilización de un gel con arginina durante 14 días mantuvo el pH neutro y el flujo salival en niveles normales sin diferencias estadísticamente significativas con el grupo control.

ABSTRACT: The effect of an arginine gel on pH and salivary flow was evaluated after fourteen days of use in women with mild demineralization. A controlled pilot clinical trial was established in which 20 women aged 18-23 years, systemically healthy and with at least one dental organ with demineralization ICDAS 3 were included, two groups: Group A / without arginine (N = 10) and Group B / with arginine (N = 10). A clinical evaluation was carried out, and a sample of unstimulated saliva was taken to determine the pH and the measurement of salivary flow at the beginning and 15 days after using the gel. Statistical analysis was performed with the GraphPad Prism version 8 program. A p <0.05 was considered statistically significant. In both groups, salivary pH was maintained close to neutrality without statistically significant differences, and salivary flow remained at normal values after using the hydrogel for 14 days, although statistically significant differences were observed in the intergroup comparison. Using a gel with arginine for 14 days kept the neutral pH and salivary flow at normal levels without statistically significant differences from the control group.

Do fluoroquinolone agents produce therapeutic benefits or harmful effects in patients with periodontitis? A systematic review and meta-analysis.

The adjunctive use of fluoroquinolone (FQ) agents in patients with periodontitis produces contradictory results. There has been no meta-analysis performed based on the evaluations of FQ use that would enable making appropriate clinical decisions. Our study aimed to evaluate, via a systematic review and metaanalysis conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines, the clinical benefits, antimicrobial effects and safety profiles of the FQ agents administered to periodontitis patients under a conventional treatment regime. Relevant databases were searched for studies published up to May 2020, with the quality and risk of bias evaluations performed on the selected studies, and meta-analyses, funnel plots and heterogeneity tests carried out based on the obtained data. Any finding of p-value less than 0.05 was considered statistically significant. Quality and the risk of bias ranged from high to low. With acceptable heterogeneity and no reporting bias, the meta-analyses showed that local or systemic FQ use produced the following results: a reduced probing depth change (ΔPD) (p < 0.00001 at ≤3 months); reduced bleeding on probing (BOP) (p < 0.00001 at 3-6 months); reduced subgingival detection of Aggregatibacter actinomycetemcomitans for up to 12 months (p-values from <0.00001 to 0.001); and an insignificant number of adverse events (p ≥ 0.05) in patients subjected to a conventional therapy as compared to those subjected to an antibiotic-free therapy. Our study found evidence to show that FQ administration provides clinical benefits and ensures antibacterial effects in periodontitis patients subjected to a conventional therapy regime.

In vitro and In vivo Synergistic Interactions of the Flavonoid Rutin with Paracetamol and with Non-Steroidal Anti-Inflammatory Drugs.

AIM/BACKGROUND: The combination of drugs with different mechanisms of action could be more effective due to an enhanced synergistic activity. The pharmacological interactions between rutin and paracetamol, and rutin and non-steroidal anti-inflammatory drugs (NSAIDs), such as naproxen, ketorolac, and diclofenac were investigated using in vitro and in vivo assays. METHODS: Individual and drug combination response curves of rutin-NSAIDs, and rutin-paracetamol (each at 0.001-0.1 mmol for in vitro studies and ranging from 1.25-100 mg/kg p.o. for in vivo studies) were evaluated in RAW 264.7 macrophages [inhibition of nitric oxide (NO) using the Griess reagent] and Balb/c mice (acetic acid-induced writhing test). An isobolographic analysis was used to assess the type of interaction between rutin and NSAIDs and rutin-paracetamol in a proportion of 1:1. RESULTS: Rutin alone and in combination with paracetamol and NSAIDs decreased NO production and the number of writhings in a concentration/dose-dependent manner. The isobolograms showed that all in vitro combinations of rutin-NSAIDs and rutin-paracetamol exerted synergistic effects. The combination rutin-diclofenac showed an interaction index of 0.17. In the in vivo assay, the combinations of rutin-diclofenac (interaction index = 0.195) and rutin-ketorolac (interaction index = 0.408) displayed synergistic effects, and the combination rutin-paracetamol exhibited additive effects. CONCLUSION: Rutin produces synergistic effects with paracetamol and NSAIDs in in vitro and in vivo assays.

Measurement of levofloxacin in human plasma samples for a reliable and accessible drug monitoring.

OBJECTIVES: Levofloxacin monitoring is recommended to obtain clinical cure and low incidence of antimicrobial resistance. During the monitoring procedure, levofloxacin should be measured in plasma samples and several assays are reported for this purpose. However, those methods do not have all of the characteristics for an accessible and reliable drug monitoring. For this reason, we develop a method that has all of the essential characteristics for levofloxacin monitoring. DESIGN AND METHODS: The procedure of validation was done in terms of Food and Drug Administration guidelines. Subsequently, our assay was applied in plasma samples obtained from healthy volunteers with a single oral administration of levofloxacin as well as patients with respiratory diseases under levofloxacin therapy. RESULTS: Levofloxacin was extracted from samples using only two precipitation steps. Our assay had a rapid run time (5min), adequate sensitivity (0.05µg/ml of lower limit of quantification), and acceptable parameters of validation. Moreover, compound identities were supported using three dimensional spectra and purities were confirmed employing similarity factors (values>900). Variable concentrations of levofloxacin in samples were observed during the application. CONCLUSIONS: Levofloxacin is successfully quantified using our method that shows reliable results, appropriate range, rapid analyses, and cost-effective measurements under a simple and easy technique while all prior methods did not have it all together. Consequently, our method is a valuable tool for routine drug monitoring. Moreover, a complete evaluation of specificity was done for levofloxacin in plasma samples for the first time. Meanwhile, the application data supported the necessity of levofloxacin monitoring.

Single dose of diclofenac or meloxicam for control of pain, facial swelling, and trismus in oral surgery

BACKGROUND: Postoperative pain associated with removal of mandibular third molars has been documented from moderate to severe during the first 24 hours after surgery, with pain peaking between 6 and 8 hours when a conventional local anesthetic is used. Dental pain is largely inflammatory, and evidence-based medicine has shown that nonsteroidal anti-inflammatory drugs are the best analgesics for dental pain. The aim of this study was to compare the analgesic, anti-inflammatory and anti-trismus effect of a single dose of diclofenac and meloxicam after mandibular third molar extraction. MATERIAL AND METHODS: A total of 36 patients were randomized into two treatment groups, each with 18 patients, using a series of random numbers: Group A, was administered 100 mg of diclofenac; and Group B, 15 mg of meloxicam. Drugs were administered orally 1 hour prior to surgery. We evaluated pain intensity, analgesic consumption, swelling, as well as trismus. RESULTS: The results of this study showed that patients receiving 15 mg of meloxicam had less postoperative pain (P=0.04) and better aperture than those receiving 100 mg of diclofenac (P=0.03). The meloxicam group presented less swelling than diclofenac group; however, significant statistical differences were not observed. CONCLUSIONS: Data of this double-blind, randomized, parallel-group clinical trial demonstrated that patients receiving 15 mg of preoperative meloxicam had a better postoperative analgesia and anti-trismus effect compared with who were given 100 mg of diclofenac after third molar extractions

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Single dose of diclofenac or meloxicam for control of pain, facial swelling, and trismus in oral surgery.

BACKGROUND: Postoperative pain associated with removal of mandibular third molars has been documented from moderate to severe during the first 24 hours after surgery, with pain peaking between 6 and 8 hours when a conventional local anesthetic is used. Dental pain is largely inflammatory, and evidence-based medicine has shown that nonsteroidal anti-inflammatory drugs are the best analgesics for dental pain. The aim of this study was to compare the analgesic, anti-inflammatory and anti-trismus effect of a single dose of diclofenac and meloxicam after mandibular third molar extraction. MATERIAL AND METHODS: A total of 36 patients were randomized into two treatment groups, each with 18 patients, using a series of random numbers: Group A, was administered 100 mg of diclofenac; and Group B, 15 mg of meloxicam. Drugs were administered orally 1 hour prior to surgery. We evaluated pain intensity, analgesic consumption, swelling, as well as trismus. RESULTS: The results of this study showed that patients receiving 15 mg of meloxicam had less postoperative pain (P=0.04) and better aperture than those receiving 100 mg of diclofenac (P=0.03). The meloxicam group presented less swelling than diclofenac group; however, significant statistical differences were not observed. CONCLUSIONS: Data of this double-blind, randomized, parallel-group clinical trial demonstrated that patients receiving 15 mg of preoperative meloxicam had a better postoperative analgesia and anti-trismus effect compared with who were given 100 mg of diclofenac after third molar extractions.

Synergism between tramadol and parecoxib in the orofacial formalin test.

The aim of this study was to evaluate the interaction between tramadol and parecoxib in the orofacial formalin test. Tramadol (10, 31.6, 56, and 100 mg/kg ip) or parecoxib (31.6, 56, 100, and 178 mg/kg ip) were administered 10 min before formalin (2.5%) injection into the upper lip to characterize the dose-response curve of each individual drug in the orofacial pain test in mice. Once the dose-response curve of each drug was obtained, an experimental effective dose 50 (ED50 ) value was determined for each drug. The tramadol-parecoxib combination was evaluated in four different groups of animals. The isobolographic analysis and the interaction index were used to evaluate the nature of interaction between both drugs. The isobologram and the interaction index showed increased in the antinociceptive effect of the combination. The tramadol-parecoxib combination produces a synergism in the second phase of the orofacial formalin test.

A novel method for measuring the ATP-related compounds in human erythrocytes.

The ATP-related compounds in whole blood or red blood cells have been used to evaluate the energy status of erythrocytes and the degradation level of the phosphorylated compounds under various conditions, such as chronic renal failure, drug monitoring, cancer, exposure to environmental toxics, and organ preservation. The complete interpretation of the energetic homeostasis of erythrocytes is only performed using the compounds involved in the degradation pathway for adenine nucleotides alongside the uric acid value. For the first time, we report a liquid chromatographic method using a diode array detector that measures all of these compounds in a small human whole blood sample (125 µL) within an acceptable time of 20 min. The stability was evaluated for all of the compounds and ranged from 96.3 to 105.1% versus the day zero values. The measurement had an adequate sensitivity for the ATP-related compounds (detection limits from 0.001 to 0.097 µmol/L and quantification limits from 0.004 to 0.294 µmol/L). This method is particularly useful for measuring inosine monophosphate, inosine, hypoxanthine, and uric acid. Moreover, this assay had acceptable linearity (r > 0.990), precision (coefficients of variation ranged from 0.1 to 2.0%), specificity (similar retention times and spectra in all samples) and recoveries (ranged from 89.2 to 104.9%). The newly developed method is invaluable for assessing the energetic homeostasis of red blood cells under diverse conditions, such as in vitro experiments and clinical settings.

Analgesic efficacy and safety of single-dose tramadol and non-steroidal anti-inflammatory drugs in operations on the third molars: a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to evaluate published randomised, double-blind, clinical trials to compare the analgesic efficacy and safety of tramadol with that of non-steroidal anti-inflammatory drugs (NSAID) in operations on the third molars. We identified eligible reports from searches of PubMed, MedLine, the Cochrane Library, Oxford Pain Relief database, Imbiomed, and Google Scholar. The full text of studies that met our minimum requirements were evaluated using inclusion and exclusion criteria with the Oxford Quality Scale. Those with a Score ≥ 3 in this scale were included and their data were extracted and analysed. Absolute increase in risk, the number needed to harm, odds ratio and 95% CI were calculated using Risk Reduction Calculator software. Each meta-analysis was made with the help of the Mantel-Haenszel random effects model, estimates of risk (odds ratio (OR)) and 95% CI were calculated using the Review Manager 5.2. from the Cochrane Library. A significant risk was assumed when the lower limit of the 95%CI was greater than 1. Probabilities of less than 0.05 were accepted as significant. The results showed that tramadol had less analgesic efficacy and an increased risk of adverse effects compared with NSAID. In conclusion, a single dose of tramadol was not as effective or as safe as NSAID for the relief of pain after operations on the third molars.